Biomedical Engineering Reference
In-Depth Information
Target product profile
Product requirements and attributes
Preformulation
Protein characterization
Molecule knowledge
Analytical/ bioassay
API critical properties
Molecular stability
Risk assessment
Formulation variables
Formulation
stabilization
Formulation DOE
Formulation development
Formulation design space
Figure
9.1.
Schematic of the formulation design space development via QbD and risk assess-
ment principles.
the critical quality attributes (CQAs). In addition, an initial risk assessment based on
preformulation knowledge is also needed to establish the criticality of those formulation
factors that are likely to influence those modifications identified to have high stability
risk. The risk assessment is essential for designing the appropriate multivariate experi-
ments to define the formulation design space by systematically optimizing the critical
formulation parameters with respect to stability properties that have a high risk of impact
on the CQAs. As a result, a commercial composition that meets the TPP requirements can
be defined based on the product stability response knowledge derived from the
formulation design space. A schematic summarizing the development of formulation
design space via the QbD and risk assessment approach is shown in Fig. 9.1.
The subsequent sections in this chapter provide further description and discussion for
each step according to the schematic as shown in Fig. 9.1 when applied to the case of
monoclonal antibody.
9.3 TARGET PRODUCT PROFILE (TPP)
To build and develop “quality” into the final product, the first step is to understand the
commercial product definition with respect to therapeutic indication, patient dosing,
