The International Conference on Harmonization (ICH) Q8(R2), Q9, and Q10 guidelines provide the foundation for implementing Quality by Design (QbD). Applying those concepts to the manufacture of biotech products, however, involves some nuances and complexities. Therefore, this paper offers guidance and interpretation for implementing QbD for biopharmaceuticals, from early-phase development steps such as identifying critical quality attributes and setting specifications, followed by the development of the design space and establishing the process control strategy; to later stages, including incorporating QbD into a regulatory filing and facilitating efficient commercial processes and manufacturing change flexibility post licensure.
CONTINUOUS VERIFICATION AND POSTAPPROVAL CHANGES
Process change is an expected aspect of pharmaceutical manufacturing. Many process changes are made as a result of increased process knowledge to keep pace with advancing technologies and improvements to the manufacturing process. When a product is first approved, its manufacturing process represents the current technology standard for manufacturing and follows the current good manufacturing practices (cGMPs) standard for regulatory compliance. After approval, market demand, technological advances, GMP standards, raw materials (e.g., resins) sourcing or manufacturing experience may require that the approved process be modified. Traditionally, these postapproval changes have required regulatory agency endorsement before implementation. The intent of this section is to propose a path forward that fosters continuous improvement and innovation, and acknowledges the extensive understanding of the manufacturing process and product (process knowledge) gained through the development of the design space or through manufacturing experience. The demonstration of extensive process knowledge in the marketing application, combined with established robust and effective quality systems to monitor manufacturing process performance, provides health authorities the assurance, and thus the allowance, to reduce regulatory oversight and the burden of postapproval change supplements while still meeting legal and regulatory expectations. The future treatment of postapproval changes will be influenced by: