Robustness and System Suitability - Analytical Validation - page 82

later.” In other words, investing a little time up-front can save a lot of time, energy,
and expense later.
During a robustness study, method parameters are intentionally varied to see if
the method results are affected. The key word in the definition is deliberate . In liquid
chromatography (LC), examples of typical variations include
• Mobile phase composition
• Number, type, and proportion of organic solvents
• Buffer composition and concentration
• pH of the mobile phase
• Different column lots
• Temperature
• Flow rate
• Wavelengt h
• Gradient variations
• Hold times
• Slope
• Length
Robustness studies are also used to establish system suitability parameters to make
sure the validity of the entire system (including both the instrument and the method)
is maintained throughout implementation and use.
Robustness is often confused with the term ruggedness , but the two terms really
have different and distinct meanings. Ruggedness was once defined in USP guide-
lines as the degree of reproducibility of test results obtained by the analysis of the
same samples under a variety of conditions, such as different
• Laboratories
• Analysts
• Instruments
• Reagent lots
• Elapsed assay times
• Assay temperature
• Days
That is, a measure of the reproducibility of test results under the variation in condi-
tions normally expected from laboratory to laboratory and from analyst to analyst.
The use of the term ruggedness , however, is not used by the ICH, but is addressed
in the guideline Q2 (R1) under intermediate precision (within-laboratory variations;
different days, analysts, equipment, etc.) and reproducibility (between-laboratory
variations from collaborative studies applied to the standardization of the method)
[2]. Because of the confusion with robustness, use of the term ruggedness (in
regard to method validation at least) is falling out of favor. References to rugged-
ness have been deleted in current USP guidelines to more closely harmonize with
ICH, using the term intermediate precision instead. Confusion still exists, however,
concerning how and when to apply the different term: robustness and intermediate