QUALITY BY DESIGN - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 93

60
50
40
30
20
10
0
Figure 5.6 Diagrammatic part-outputs of initial and final a risk assessments to show the
impact various unit operations may have on a CQA. (Dotted line shows level of acceptable
risk). ( See insert for color representation of the figure .)
It is important to note that design space is optional and normally multidimen-
sional. Many attributes and parameters will have some interrelation with each
other and therefore the design space should take into account the basis of these
interactions and their boundaries. Having said this, it is not necessary to investi-
gate the limit of every boundary as it may be expensive in time and resources to
carry out this work. Where, through prior knowledge, it is known that a particular
unit operation has a wide design space, then, after assessing the appropriate risk to
product quality, perhaps minimal or no experimental work might be carried out.
It is also important to note that it is not essential to demonstrate the edge
of failure of design space, unless of course there is a need to operate very
close to this edge. Companies should assure themselves that the most important
boundaries of design space have been assessed to understand where further data
may be needed.
ICH Q8R2 [1] gives some examples of design space and their Figure 5.2c is
shown below (Fig. 5.7):
Establishing the control strategy is probably the most important step of all
the QbD steps. Control strategy is defined in Q10 [3] as, “ a planned set of
controls, derived from current product and process understanding that ensures
process performance and product quality. The controls can include parameters
and attributes related to drug substance and drug product materials and compo-
nents, facility and equipment-operating conditions, in-process controls, finished
product specifications, and the associated methods and frequency of monitoring
and control .”
This wide definition illustrates the importance of putting in place all the
controls that may be necessary at each stage of manufacture to assure the final
drug product CQAs are met. The term control in this case may include a wide