Quality by Design for Biotechnology Products—Part 1 - A PhRMA Working Group's advice on applying QbD to biotech. - BioPharm International

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Quality by Design for Biotechnology Products—Part 1

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.


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