Instrument validation

A test of linearity as applied to instrument validation is given in Ref. 

In cases where a mixture has a large number of components, or pure standards are not available, published retention data must be consulted. The uncorrected retention time, tR (p. 86), is not suitable for this purpose because it cannot be compared with data from different columns and instruments. Valid comparisons can be made using relative retention data which are dependent only on column temperature and type of stationary phase. An adjusted retention time, / R, is first obtained by subtracting from tR the time required to elute a non-retained substance such as air (Figure 4.26)... 

Crowther, J. B., Jimidar, M. L, Niemeier, N. and Salomons, P., Qualification of Laboratory Instrumentation, Validation and Transfer of Analytical Methods. Chapter 15. In Analytical Chemistry in a GMP Environment, Miller, J. M. and Crowther, J. B., Eds., John Wiley Sons, Inc., New York, 2000. 

Full instrument validation should be regularly repeated at least half a year routinely, even if routine measurement was successfully performed every day. Unscheduled validation is recommended if valuable samples will be analyzed next, if the lamp exceeds its specified lifetime, or if unusual performance data are obtained although validated methods were used. 

Instrument validation should show that an instrament is able to perform according to its design specification. This can be done for example by means of calibration or performance checks [Eurachem Guide Fit for Purpose]... 

In recent years, tremendous efforts have been put forth by many organizations to address the validation of a wide variety of laboratory instruments of varying complexity. Instrument validation-related topics have been discussed at great length... 

The fundamental purpose of laboratory instrument validation is to provide assurances that the instrument is suitable for its intended use. The assurance is supported by documented evidence that the system consistently performs according to predetermined specifications for its intended applications. 

This chapter provides an overview of laboratory instrument validation for GMPs and GLPs. The term GxP is used as a general referral to GMP and GLP. The focus of this chapter is on the validation of COTS instruments using a scalable approach. 

Conceptually, a life-cycle approach to laboratory instrument validation can be divided into four phases, as shown in Figure 1. 

References of Relevant Information List the internal and external instrument validation guidance documents, compendial reference methods, qualification testing, and related SOPs for validation. 

The terms instrument qualification and instrument validation are sometimes used indiscriminately. In this chapter, the term qualification refers to the site preparation and the testing employed to demonstrate that the instrument is properly installed in a suitable environment and the performance meets the predetermined specifications for its intended use. Qualification is a part of the whole validation life cycle. Validation refers to the process to provide assurance that the instrument is suitable for the intended application throughout the lifetime of the instrument. Installation qualification (IQ), operation qualification (OQ), and performance qualification (PQ) are performed to provide evidence that the user requirement specifications (URSs), functional requirement specifications (FRSs), and design qualification (DQs) have been met. The sequence of requirements setting and qualification events as well as the relationships between IQ, OQ, PQ and URS, FRS, and DQ are generally illustrated by the V diagram shown in Figure 2. Installation qualification demonstrates the fulfillment of the DQ. Similarly, OQ demonstrates the fulfillment of the functional requirements and PQ demonstrates the fulfillment of the user requirements. 

OPCW procedures. After validation and packing has been completed, the Office of Internal Oversight (OIO) audits the process of instrument preparation and issues a certificate for on-site use. The OPCW Laboratory and the OIO are accredited for this process. The instrument is to be operated exclusively by AC inspectors who are trained and authorized for this task. At least one of the ACs participating in the inspection will assist during the instrument validation and packing process at the OPCW Laboratory. 

In a series of papers, the group of Volmer [130-132] studied the analysis of azaspiracid biotoxins. Ultrafast and/or high-resolution LC of azaspiracids on monohthic LC columns was evaluated [130]. Chromatograms of five azaspiracids on a 100-mm and a 700-mm monolithic column are shown in Figure 14.11. Fragmentation of azaspiracids in MS-MS on ion-trap and triple-quadrupole instruments was studied as well [131]. The interpretation was confirmed using accurate-mass data from a Q-TOF instrument. Validation of a quantitative method for AZA-1 was also reported [132]. The LOQ was 5 and 50 pg/ml extract using a triple-quadrapole in SRM mode and an ion-trap instrument, respectively. 

P.K.S. Blay, S. Brombacher, D.A. Vohner, Studies on azaspiracid biotoxins. III. Instrumental validation for rapid quantification of AZA-I in complex biological matrices. Rapid Commun. Mass Spectrom., 17 (2003)2153. 

Calibration is used here to describe whatever process is used to relate observed spectral frequencies and intensities to their true values, and validation is a procedure to verify the calibration and determine the magnitude of experimental error. Raman spectroscopy is a demanding technique in terms of reproducibility and accuracy and involves a variety of instrumental configurations. Calibration is often the source of irreproducibility and inconsistency in reported Raman spectra. This chapter is divided into four general sections frequency calibration (10.2), response function calibration (10.3), absolute response calibration (10.4), and a summary of procedures (10.5). For each section, standards and procedures for instrument validation are considered. 

Instrumental validation in capillary electrophoresis and checkpoints for method validation 15... 

The majority of analytical processes in regulated environments rely on computer control for automation and for data capture and evaluation. It is therefore important that not only is the instrument validated but also the computer and operational software. Validation of software is more complex than hardware validation, especially since source codes for many analytical processes can run to several hundred thousand lines. In this case the responsibility for validation still remains with the user, who should have the assurance that the computer system has been validated during and at the end of the DQ phase. The vendor should provide documentation with a declaration that the software has been validated to these or similar guidelines to ensure software quality standards. Further, the vendor should provide access to the source codes if required by the user. 

Quality control Quality assurance Instrument validation... 

An integral aspect of instrumentation validation is that not only should all instruments be calibrated when first installed but that they should also be recalibrated at fixed or variable intervals. These intervals should be established on some sensible basis that is intended to ensure that instrumentation will meet its required accuracy specifications throughout all periods of usage. 

To perform the instrument validation and determine analytical figures of merit, stock standard solutions of dimethyl mercury, methyl mercury chloride, and ethyl mercury chloride were prepared by dissolving the pure compounds in HPLC Grade toluene. Each solution was prepared to approximately 100 jug/g of the mercury compoimd. These solutions were obtained... 

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