Chemistry Reference
In-Depth Information
Initial risk
assessment
Identify material
attributes and
process parameters
to be studied
with ranges
Identify
potential
CQAs
Identify QTTP
Select
thresholds
for criticality
Design
experiments
Execute
experiments
Analyze and
write reports
Determine
material/
parameter
criticality
Select design
space and
control
strategy
Complete
submission
support
documents
Finalize
process
models
Finalize
regulatory
submissions
Figure 11.2.
Quality by design process
ow.
11.2 THE STRATEGY OF QUALITY BY DESIGN
No doubt many readers of this topic will already be acquainted with the methodical,
systematic approach to formulation development called quality by design [31
37].
However, QbD is so central to our strategy and our day-to-day operations that it is
worthwhile to describe the approach here in some detail as a prelude to the case study that
follows.
At the heart of QbD is scienti
-
c understanding of both the product and the process of
development
ciently rigorous to allow development teams to set
predefined objectives and meet them with thorough risk management. The anticipated
payoff is a better product, as well as a more reliable development process with fewer
unforeseen failures, dead ends, and wasted time. This process, which was originally
laid out in the ICH documents Q8, Q9, and Q10, is summarized by the
—
understanding suf
flow diagram
in Figure 11.2.
As the
gure re
ects, QbD begins with a quality target product pro
le, or QTPP,
which is derived from a clinical target product pro
le that states the clinical goals of the
product. The QTPP lays out the quality-related goals that the product will have to meet in
order to reach the clinic. It could include the desired dose size, the limits on impurities
and degradation products, and the shelf life in commercial packaging. Table 11.2 lists the
de
nition of key terminologies used as the foundation for the material and process
criticality analyses.
With the QTPP in hand, a development team can proceed to step 2 of QbD, which
consists of de
ning critical quality attributes, or CQAs. The CQAs are the characteristics
that need to be within a certain range or to display a certain distribution in order for the
