Biomedical Engineering Reference
In-Depth Information
10
APPLICATION OF QbD
PRINCIPLES TO BIOLOGICS
PRODUCT: FORMULATION AND
PROCESS DEVELOPMENT
Satish K. Singh, Carol F. Kirchhoff, and Amit Banerjee
10.1 INTRODUCTION: QbD IN BIOLOGICS PRODUCT DEVELOPMENT
The inherent complexity of biologics presents a challenge in the application of QbD and
design space concepts. The link between product/molecule attribute and clinical
performance is not always well understood. The heterogeneity of the product makes
it difficult to precisely measure all the attributes of the molecule. It can be difficult to
define the quality attributes (QAs) that are truly critical to safety and efficacy.
Consequently, the focus shifts toward using clinical experience and maintaining process
consistency. Similarly, the functional relationship between process parameters and
quality attributes may not be readily defined.
The development of a stable formulation for a biologic therefore involves account-
ing for the inherently complex structure of the protein and the multiple degradation
pathways it may undergo. A compromise among competing degradation pathways may
be required to develop an optimized formulation (e.g., acid hydrolysis and deamidation).
A large body of knowledge has been generated that can aid the formulation scientist in
this task, and a number of summaries and reviews have been published (see, for example,
Refs [1-3]). For biologics, heterogeneity of the bulk drug substance is the rule
rather than exception, and the upstream and downstream processes are a major source
