ABSTRACT
The major objective of product optimization is to ensure that the product selected for further development (the intended commercial product) is fully optimized and complies with the design specification and critical quality attributes (CQAs) described in the Target Product Profile and Product Design Report (refer to chap. 5). The traditional approach to product development described in the original version of this book emphasized that the following key outputs should be obtained from this stage of development:
l A quantitative formula defining the grades and quantities of each excipient and the quantity of candidate drug
l Defined pack l Defined drug, excipient, and component specifications l Defined product specifications
Although these are all still important, a paradigm shift led by the regulators in how products should be developed has added another dimension to the key outputs from product optimization. A series of quality-by-design (QbD) regulatory initiatives, including process analytical technology (PAT) and the ICH guidances [ICH Q8, pharmaceutical development; ICH Q9, quality risk management (QRM); ICH Q10, pharmaceutical quality systems (PQSs)], have been introduced to change the outputs from product optimization. The emphasis has changed from the need to demonstrate that the product will consistently meet relatively tight specifications to a new situation of being able to demonstrate that the product is controlled within a broader “design space.” Product optimization studies are conducted to determine the critical formulation attributes and critical process parameters and to assess the extent of their variation on quality attributes of the drug product, and hence to define the design space. Once this is defined, then changes within that design space should not require further regulatory approval. This QbD approach encourages the need for a greater scientific understanding of the product/process and to firmly link product development with manufacturing design. As continuous quality verification is built-in with PAT-based manufacturing and process control strategies, traditional end-product testing and tight product specifications should become less significant and the desired state of “real-time release” should be possible.
