Biomedical Engineering Reference
In-Depth Information
Figure
9.6.
Concept of formulation design space. (See the insert for color representation of this
figure.)
critical formulation variables. Furthermore, this information forms the knowledge
base for selecting a commercial solution formation with sufficient robustness that is
likely to meet the shelf life stability requirements. To illustrate the formulation design
space concept, projection of the acceptable range of the two critical formulationvariables
that meet all the specified stability criteria is shown in Fig. 9.6. The size and shape of the
“design space,” which is depicted as the “white region” in Fig. 9.6, depend on the
combination of different stability criteria projected for the various critical analytical
properties.
9.9 SELECTION OF SOLUTION FORMULATION COMPOSITION
The solution formulation composition is defined by optimizing stability properties with
respect to degradation pathways that have high risk of impacting the CQA. The selection
is based on the DOE results and statistical modeling analysis, as well as preformulation
characterization and forced degradation study results. In particular, experimental
results are used to justify and mitigate the formulation risk factors identified with the
Ishikawa diagram as shown in Fig. 9.4. For example, the rationale of selecting the
solution formulation composition for a typical case example of antibody is summarized
in Table 9.4.
The next step is to place the proposed commercial formulation on stability at
multiple temperature conditions to evaluate the effect of long-term real-time storage. To
support potential dosing levels for later stage clinical studies, stability studies are set up
over a range of concentrations. In addition, different combinations of container closure
systems are also included to delineate any potential incompatibilities. The real-time
