Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 19
tested one at a time in a serial fashion, QbD applies
a systematic methodology resulting in a full under-
standing of various sources of method variation
and control of the method.
The development process starts out by defining
the analytical target profile (ATP). For most ana-
lytical methods, the assay ATP should minimally
include a basic statement with respect to method
accuracy (bias) and precision (variance). For in-
stance, the procedure must typically be sufficiently
accurate to measure concentration of the analyte
within 95–105% of the nominal concentration and
precise based on relative standard deviation (RSD)
values of 3% or less. Once a target profile has been
defined, it is then time to identify an appropri-
ate analytical technology that will deliver on the
target profile requirements. The type of analytical
technique selected will be dependent on the prod-
uct attribute to be measured and the needed level
of accuracy and precision. Table I provides some
examples of product quality attributes and corre-
spondingly applicable analytical methods.
Performing risk assessment
Once the appropriate method is selected, it will be
necessary to start scouting assay conditions. For
chromatography, identifying the correct column is
crucial to assay performance. For this reason, sev-
eral columns with varying characteristics, such as
carbon loads for reverse-phase, pore-size and silica
modification for size-exclusion chromatography, as
Figure 2: Experimental design approach based on number of variables.
The risk analysis should include
materials needed for method
execution, equipment, operators, and
various method elements.
