Chemistry Reference
In-Depth Information
As was stressed earlier in the chapter, our group developed the formulation for
telaprevir within the QbD framework. As the opening step, the quality target product
pro
le for telaprevir had speci
ed that the commercialized drug should be
an immediate-release tablet;
stable during 24 months of shelf storage;
orally administered;
bioavailable;
safe;
ef
cacious;
easily distinguishable from other medications.
With these requirements as the starting point for telaprevir
'
s design, the project team
moved on to de
ne the CQAs for SDD and drug product (coated tablet). These attributes
and their anticipated impacts on quality, safety, or ef
cacy are presented in Table 11.3.
11.3.2 Conceptual Approach to Telaprevir Process Design Space
Development
Once telaprevir CQAs were identi
ow as
depicted in Figure 11.2 was executed to establish the design space for telaprevir drug
product. For the purpose of illustration, the process from initial risk assessment to the
development of design space is described, focusing on the particular tablet (drug product)
CQA of dissolution.
For tablet CQA of dissolution, an initial risk assessment was performed on tablet
manufacturing process and materials to determine which process steps and materials
potentially afford control of telaprevir tablet CQA of dissolution. If a material, process
parameter, or in-process control in a particular step can potentially impact the CQA of
dissolution, then that material and/or step is potentially critical, and is further investi-
gated via a detailed criticality analysis. The initial materials risk assessment is performed
to evaluate the potential of CQA of dissolution to be impacted by variability of the
material within the incoming materials
ed (as shown in Table 11.3), the QbD process
cations. For example, if lot-to-lot varia-
bility in the particle size of telaprevir SDD could potentially affect tablet dissolution, then
telaprevir SDD material has the potential to impact the dissolution CQA of tablet. The
risk assessment summarized in Table 11.4 is a preliminary assessment of the potential of
particular materials or process steps to affect tablet CQA of dissolution. If a material or
process step is deemed potentially critical, then further experiments and analysis should
be performed before reaching a
'
speci
final conclusion on the criticality of the material or
parameter.
The initial risk assessment of materials and process steps (Table 11.4) suggested that
telaprevir SDD is potentially critical material. In addition, all the processing steps are
determined to be potentially critical as each impacts the tablet CQA of dissolution. All
potentially critical unit operations were studied to determine potential critical and key
processing parameters by performing design of experiments. Table 11.5 lists parameters
