The European Medicines Agency, along with the US FDA, have released a second question-and-answer document intended to provide guidance to industry on the concept of quality by design.
In March 2011, EMA and FDA announced the launch of a pilot program they said was intended to allow them to better communicate review findings with respect to QbD elements of applications chosen for review.
In August, EMA and FDA released a question-and answer document with advice on several aspects of the QbD process based on what they had learned through their participation in the pilot to date.
At the time, both regulators said additional Q&A documents would be forthcoming, and now a second Q&A document has been released. The document contains nine questions and answers, including:
• Why would a design space be verified during the product lifecycle? (There are risks inherent in scaling-up or making new model assumptions, and it is necessary to understand these risks.)
• What is the purpose of design space verification at commercial scale? (to demonstrate control over the product and its quality)
• How is a design space initially developed and verified at commercial scale? (based on experiments conducted at laboratory or pilot scale, which requires subsequent validation at larger scales)
• How can a design space be verified at commercial scale? (It is not necessary to repeat at commercial scale the experiments initially conducted to define a design space at lab or pilot scale, but should be guided by the results of risk assessments.)
• How should design space verification protocol be addressed in the submission? (General and specific requirements for both EMA and FDA are explained.)
• What if unexpected results/events are obtained during the design space verification studies? (The results should be studied and, if necessary, reported to regulatory authorities.)
• How can a design space be verified at commercial scale for biological products? (The principles are the same for both chemical and biological products.)
• What is the difference between process validation and design space verification? (Process validation demonstrates consistency of the process at normal operating ranges, design space verification demonstrates that scale effect and or model assumptions are under control in the new area of design space and do not affect product quality.)
• How should design space verification approach be addressed in the pharmaceutical quality system? (Firms should have a written plan for when and how to evaluate the need for design space verification.)
