Software validation

A number of computer software packages are available to the analyst to assist in the planning and execution of both method development and validation experiments. The attraction of these systems is that they can automate the validation process from planning the experiment to test execution to the presentation of the data in a final report form. 

Other chromatographic systems snch as DryLab 2000 Pins from LC Resonrces (http //www.lcresources.com) incorporate aspects of method development and validation throngh simnlation software combined with actnal experiments to determine optimal operating conditions. This system is designed to generate efficient method development and method optimization experiments. Resnlts from these experiments can be nsed for the evaluation of robusmess as part of the validation for methods developed using this type of software. 

The anthor wonld like to thank Lane Gehrlein, Phil Palermo, Michael Dong, and Mike Brockner of Pnrdne Pharma, LP for their help in the preparation of this chapter. 

International Conference on Harmonisation (ICH) Q2A, Text on validation of analytical procedures March 1995. 

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Validate software used for measurement purposes or for driving measuring equipment. 

Software verification consists of tasks performed to evaluate if the software is performing desired tasks and providing desirable results. Software verification is part of software validation. Software testing is one of the many verification activities intended to confirm that software development output meets its input requirements. Other verification activities include various static and dynamic analyses, code and document inspections, walkthroughs, and other techniques [14]. 

It is important to note that, although the tables of experimental designs in this chapter show an orderly progression of experimental conditions, when the experiments are done, the order must be randomized. A random order can be generated in a spreadsheet, or if statistical or validation software is used, the program might randomize the order. Randomizing the order of experiments is the best way to confound uncontrolled effects and should always be employed. 

Derived from Good Data from Validated Software... 

Validation of computer systems—The role of QA is of particular importance with respect to complying with Part 11, related to electronic records and computer validation. Clinical QA must ensure that any computerized system associated with a study is adequately validated and that the documentation for that validation is concise, complete, and available for audit. Clinical QA must provide the appropriate guidance to both the validation and information technology groups to ensure that clinical studies are not invalidated because of inadequately validated software or hardware. 

Your response fails to trace back to source code, and the related software development cycle which establish evidence that all software requirements have been implemented correctly and reliably and has been validated. Software is validated in its controlled development and in control of ongoing maintenance of the software and its documentation throughout its lifetime. [FDA Warning Letter, 2001]... 

The firm did not validate software for electronic records and electronic signatures. [FDA Warning Letter, 2000]... 

It is advisable to use a color-coded labeling system to keep track of the test stages. In our case, a yellow spot was added after successful heat cycling with test software loaded, and a green spot half covering the yellow spot was added once the validated software had been loaded and the board tested successfully no device could be shipped unless both spots are present. The manufacturer will be expected to supply a certificate of conformity for the devices produced and packed with each batch. 

Statistical tests should only be carefully (directly) applied as acceptance criteria due to the small number of data normally obtained. Sometimes, because of abnormally small variabilities in the analytical series, differences are identified as significant which are of no practical relevance. In addition, when comparing independent methods for the proof of accuracy, different specificities can be expected which add a systematic bias, thus increasing the risk of the aforementioned danger. The analyst must decide whether detected statistical differences are of practical relevance. On the other hand, a large variability can also obscure differences which are not acceptable. If validation software is used, it must be flexible enough to meet these precautions. ... 

In all levels, validation software can be used to standardize and to improve the efficiency of documentation of the data and calculations. However, it should be flexible enough to allow the necessary case-by-case (or type-by-type) design of the validation. ... 

Data may be organized by type of data, such as adverse events, laboratory data, demography, physical exam, etc. Since many of these categories of data exist across clinical trials, standard file structures can be designed and implemented. This standardization allows for the reuse of validated software as well as facilitates the pooling of data across studies for use in project safety summaries and other data reporting across studies. 

Tests should be developed for each subsystem, and each subsystem should be validated. Again, the vendor should provide validated software to automatically execute these tests. An example was shown above for chromatographic data systems. 

WinGX WinGX suite for small molecule single crystal crystallography, L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837 838 Includes and links to wide variety of validation software including Platon... 

The computer-controlled system acquires raw spectral data within the range of 200-400 nm at specified time intervals, calculates the results with the use of validated software, and stores the data in a secured computer database. Except for the dissolution apparatus itself, the system contains no moving parts. The spectral data can be corrected for turbidity-related scatter with the use of either a simple baseline subtraction or a second-derivative-based algorithm, and test results and/or profiles can be viewed in real time. 

Various types of validation generally required in biopharmaceutical manufacturing include process validation, facility and equipment validation, analytical method validation, software validation, cleaning validation and expression system characterization. Combined with other elements of cGMP, including lot release testing, raw material testing, vendor quality certifications, and vendor audits, the quality of product can be consistently assured. 

The nature of expert systems and their development process presents particular difficulties for the application of the traditional method of validating software against comprehensive pre-specifications, since the final level of operation of an expert system is difficult to pre-determine. Testing by measuring the degree of comparability of the system s performance to the performance of human domain experts, by using a representative set of problem cases, is more practical and more in tune with the definition of expert systems. 

The validation software also reports on solvent-accessible voids (van der Sluis and Spek, 1990) in the stmcture. Such voids might include disordered solvent that went... 

Reflection data can be checked for completeness when made available to the PLATON validation software as an FCF file along with the CIF file. Inadequate data collection procedures may result in an incomplete survey of the reciprocal lattice. Data collection on a CCD or image-plate based diffractometer may require more than one scan in order to avoid a cusp of missing data. ... 

It is much easier to detect and correct for overlooked problems with a crystal structure during or immediately at the end of an analysis than during the publication process. Early on structure validation also allows the investigator to go back to the experiment, when appropriate, for the gathering of additional data. Validation software should be available on the platform where the structure is solved and refined or accessible on that platform through the web. 

The Omnic software controls the data collection, data reduction and validation software, ensuring clientele of high quality analytical data. 

The validation software ensures that the instrument is operating within the required specifications. 

A quality assurance programme is required to be established and implemented to cover items, services and processes that affect safety and are within the scope of this Safety Guide (Ref. [1], paras 3.14-3.16). The quality assurance programme is required to be implemented to ensure that data collection, data processing, studies, analyses and qualification, code validation (software) and verification, and other activities necessary to meet the recommendations of this Safety Guide are performed correctly [11,12]. 

Equipment Timing of validation Who will do the validation Modes of operations to be validated Abnormal conditions foreseen Safety-related software to be validated Software specification references Expected results pass/fail criteria... 

This is intended for correction, enhancement, and adaption in validated software. Major issues involved shall include but not be limited to ... 

Moreover, the use of drying curves enables detection of the main governing mechanisms that control the heat and mass transfer phenomena and, in this way, enables one to determine the main input physical variables for setting up and validating software for the control and monitoring of the freeze-dryer (shelf temperature or total gas pressure). 

Current methods of validating software for autonomy in aerospace systems involve a series of expensive evaluation steps to heuristically develop confidence in the system. For example, UAV flight software typically requires validation first on a software simulator, then on a hardware-in-the-loop simulator, and then on flight tests. Fault-management systems continue to operate during flights, as required. 

Starting with validated software and instrument qualification a validated analytical method is developed using the qualified system. Finally, total validation is achieved by defining system suitability. The analytical chemist is mostly concerned with steps (Hi) and (iv), but he might be (rightly) suspicious regarding developments beyond his field of vision. 

Schneidewind, N. (1992). Methodology for validation software metrics. IEEE Transactions on Software Engineering 18(5), 410 22. 

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