LaChrom

2000 When operating according to quality management systems (e.g. GMP or GLP), validation of the
procedures used is of the utmost importance. However, this process including the compilation of
the validation report is often tedious and time-consuming. The Validation Manager is a valuable,
time-saving aid, which has been spec-ially developed to do all of this and provides the analyst with
the necessary calculating power whilst at the same time offering ease of operation.

A genius method in validation

■ Universally accepted
The Validation Manager is based on the guidelines for the validation of analytical methods as established by
the European and US pharmacopoeias (EP and USP), the International Standardisation Organisation (ISO) and
the International Conference on Harmonisation (ICH).
■ Easy operation
A standard Windows® menu structure and on-line help functions make working with the software very easy.
Even explanations of all calculation methods and algorithms are provided. Chromatography data can be
imported direct from the LaChrom® D-7000 HPLC System Manager Software – a function that saves time and
helps to prevent errors. In addition, EXCEL™ or WORD™ tables can be imported.
■ Versatile
Depending on the application and the analytical method used, the validation of different method
characteristics is required. The Validation Manager enables such characteristics to be flexibly selected and
separately calculated and validated. A separate report is compiled for each of the characteristics selected. It
can also be designed to meet individual requirements. Moreover, the validation report can be exported to
Microsoft® WORD™ 97 and subsequently edited in the desired format and language.
Table and column headings can be adapted to the requirements of the various analytical techniques;
headings, descriptions and units can be entered by the analyst. There is also sufficient space for comments,
e.g. for descriptions of procedures or justifications of decisions taken. Statistical calculation methods and
applied confidence levels can be selected as well.
This high degree of versatility thus enables the Validation Manager to be used for the validation of
practically all analytical methods, technical tests and measurement procedures.
■ Added confidence
In addition to the calculation and statistical
methods described, the Validation Manager
provides further statistical aids for the
evaluation of validation results. E.g. for
series of values, besides the outlier tests an
additional statistical test is provided, by
which the normality of distribution can be
checked. If this test fails, bad validation
results can be explained by a not normal
distribution of the values.

Selection of the method characteristics to be studied

 Reliable validation results –
statistically proven
■ Specificity
Confidence in the specificity of the analytical method can be assessed
visually, subsequent to graphical super-imposition of the analytical results
obtained (e.g. chromatograms). Chromatograms can be directly imported and
overlayed from the D-7000 HPLC System Manager Software. On the other
hand, diode array detector data, mass spectroscopic data or data from other
analytical systems can be entered as graphic files.
■ Precision
You can be completely confident in the precision of a method when
"Validation Manager" has determined this by calculating the coefficient of
variation for each set of data and by calculating the repeatability, the
intermediate precision and/or the reproducibility. The homogeneity of the
sets of values can be checked by using either the Dixon or Grubbs outlier
test and the homogeneity of the variances can be checked using the Cochran
or Bartlett test.
■ Detection limit and quantitation limit
The Validation Manager provides three different methods for estimation of these
parameters. Two of these are based on the determination of signal-to-noise
whilst the third uses the calibration curve and the calculated residual variance.
Validation Manager provides an extra calculation function for validation of
the quantitation limit.
■ Linearity
For verification of linearity the calibration curve is compiled using linear
regression in conjunction with the least squares fit. Subsequently, the linearity
is statistically checked by establishing the presence of a significant slope and
by testing the validity of the calibration curve. A plot of the residuals provides
additional information for assessing this method characteristic.
■ Accuracy
Accuracy of the method is verified by its determination either at the target
concentration or over the entire working range. Using the Student Test, the
Plot of residuals for evaluation of linearity distribution of recovery rates, as calculated from the theoretical and measured
concentrations, is checked as to whether it includes the 100% value.
■ Robustness - Inter-laboratory trials
The robustness of a method is assessed by establishing the effect of defined
minor alterations to the method on precision and accuracy of the analytical
results obtained.
On the other hand, the reproducibility of a method is determined by inter-
laboratory trials, whereby the precision and accuracy of the data obtained
from several laboratories is calculated.
LaChrom
2000

Dramatic time-savings in
compiling the validation report

■ After entering data and performing calculations for the method

characteristics selected, the Validation Manager automatically
prints a validation report. Its contents are selectable. In the
most comprehensive form it contains
■ A description of the calculation methods
■ applied, including mathematical formulae
■ Documentation of the input data
■ Documentation of the calculated data
■ Comments
■ Validation results and their evaluation.

■ Input data, calculations and results can

be supplemented by the analyst's own comments. Form and
language of the report can be adapted by exporting it as a
WORD™ 97 document. This validation report can be submitted
directly to the authorities as a
final method validation document.
■ Validation Manager – for the time-saving validation of
analytical procedures according to international guidelines.

Minimum PC configuration required for Validation Manager:

586 processor, 100 Mhz, 16 Mbytes RAM, IBM compatible, Microsoft® Windows 3.1x™,
Windows 95™, Windows NT™ 3.51 or higher.

Ordering Information
Cat. No. Designation
1.18988.0001 Validation Manager

Validation Manager is including as a free "Extra" in the LaChrom 2000

System Package for research and method development

LaChrom® is a registred trade mark of Merck KGaA

Merck KGaA
64271 Darmstadt / Germany
Telefax: +49 6151 - 72 74 95
http://www.merck.de/chromatography