The design space is defined as the multidimensional combination and interaction of input variables (for example, material attributes) and process parameters that have been demonstrated to provide assurance of quality.¹ Working in the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.

It is important to understand that the discussion document illustrates just one of many possible approaches to achieve the ultimate goal of QbD. Therefore, the document must not be taken as 'a standard recipe' for product development nor as a complete example for an actual submission document.

Products and manufacturing processes should be designed to manage variation. Formulation and process design in combination with risk management principles should be applied to ensure QbD is achieved during development and manufacture, yielding good understanding and control of variation. Manufacturing processes based on QbD are a means to mitigate the risk of variable product unit quality. Use of design space (ICH Q8 ), QRM (ICH Q9), and PAT principles, tools and practices, enables QbD to achieve the desired state.

The Mock P.2 submission

The Mock P.2 document gives examples of how quality can be built-in during formulation and process development. It includes the following concepts:

• The use of models and algorithms.
• The use of in-line and at-line tools.
• Using prediction models to establish the design space.
• Design space not requiring 'edge of failure' — a process parameter value that, if exceeded, means adverse effect on the process output or product quality.
• Linking control strategy to design space.
• The use of QRM principles.

In particular, it describes how enhancement of process understanding can be applied using prior knowledge and iterative application of QRM principles based on the target product profile during the design and development process.

The document is complemented by a 'mock' section P.3.3 excerpt outlining the process control strategy proposed for routine manufacture, which is based on the knowledge and understanding available and linked to a QRM review of all information available.