ESTABLISHING CRITICAL QUALITY ATTRIBUTES, SPECIFICATIONS, DESIGN SPACE, AND CONTROL STRATEGY FOR A BIOTECH PRODUCT
QbD is centered on the patient.Understanding the patient's needs for managing his or her disease state helps define the QTPP.
Safety, efficacy, convenience, compliance, and cost effectiveness of the product must be considered. Next, CQAs of the product
are identified, based on the understanding of the impact of various quality attributes on the safety and efficacy of the product.
The initial assessment is based on molecular design and known attributes of the molecule. These include not only a comprehensive
understanding of the molecular structure but also data collected from clinical and nonclinical studies that have been performed
with the molecule and with other relevant molecules, as well as other applicable published knowledge. This process of assessing
quality attributes and determining their criticality is ongoing, and is revisited continuously throughout the product lifecycle
as more data become available. These data are also used to set appropriate specifications for the drug substance and the drug
product, and to develop the overall control strategy.
Figure 1. Steps taken toward establishing critical quality attributes, specifications, design space, and control strategy
The CQAs are also used to design the molecule and the manufacturing process to meet patient needs and endpoints for safety
and efficacy, as well as to control process and product quality. Further, the process is optimized and characterized, and
the cumulative data set is used to define the critical process parameters, process design space, and the process control strategy,
which together ensure that appropriate quality is maintained and variability is managed during the manufacturing, storage,
and distribution of the product. This approach is schematically illustrated in Figure 1. A more detailed discussion of these
steps is presented below.
Applying QbD Early in Development
Products that are early in the development process are in a unique position to participate fully in prospective QbD during
development. Consequently, companies may be able to develop an efficient, cost-effective commercial process for such products,
and benefit from a more flexible reporting mechanism for changes to the application after approval. This situation is expected
to provide an opportunity for manufacturing to incorporate new technology more quickly and easily and to make changes within
the design space without regulatory agency review and approval.
Products in early stages of development usually have a limited amount of manufacturing history and limited commercial-scale
experience. As commercial-scale manufacturing data are gathered post-approval, new knowledge can be continuously integrated
into the pre-approval understanding. The resulting comprehensive knowledge can then be used to support process changes and
the assessment of their potential impact on critical quality attributes based on all available lifecycle data.
Anurag S. Rathore, PhD, is a consultant, Biotech CMC Issues, and a member of the faculty in the department of chemical engineering at the Indian Institute of Technology. Rathore is also a member of BioPharm International's Editorial Advisory Board.
Articles by Anurag S. Rathore, PhD
John Towns is the senior director of global CMC regulatory affairs at Eli Lilly and Company. Towns is also the chair of the Quality by Design Working Group of the PhRMA Biologics and Biotechnology Leadership Committee
Articles by John Towns
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