eBook: Analytical Method and QC Testing Strategies for Biologics Production - 16

Critical Quality Attributes
Assessment and Testing Strategy
for Biotherapeutics Development
Christine P. Chan
Introduction
Criticality assessment of product quality attributes
forms the foundation of the Quality by Design (QbD)
approach to drug development. This systematic
approach to product development emphasizes product
knowledge and process understanding along with
process control based on sound science and quality
risk management. Due to complexity of the molecular
structure as well as the manufacturing process,
development of biotherapeutics remains challenging.
It is often difficult to fully evaluate the impact of the
large number of quality attributes as related to safety
and efficacy. The effects of manufacturing process
parameters and material attributes on product quality
variations are also difficult to fully characterize. For
robust manufacturing operations, it is important that an
integrated control strategy is developed and improved
over time based on systematic process characterization
along with implementation of appropriate risk
assessment and mitigation throughout the product
lifecycle. This article discusses the key concepts of
critical quality attributes (CQAs) risk ranking based on
prior knowledge and gathering of structure-function
relationship information, consideration of process and
stability impact on CQAs, and evolving the analytical
testing panel as part of the integrated control strategy.
CQA Criticality Assessment
CQA is defined in ICH guidance Q81
as " a physical,
chemical, biological or microbiological property or
characteristics that should be within an appropriate
limit, range, or distribution to ensure the desired
product quality. " Typically, CQAs for a given product
are defined early in development prospectively
based on the quality target product profile of the
biotherapeutic, and progressively refined as additional
product knowledge is gained over time with extensive
analytical characterization, animal studies and
expanded clinical experience.
Listing of potential CQAs
Identification and selection of CQAs begins with
the assembly of a comprehensive list of relevant
product attributes that may have potential impact on
product quality. The ultimate objective is to establish
linkages between specific product attributes of the
biotherapeutic to the expected clinical performance.
For complex biologicals, this list may be long and
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eBook: Analytical Method and QC Testing Strategies for Biologics Production

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