PAT R&D efforts in pilot plant (proof of concept and suitability for application in manufacturing)

What should be documented to justify suitability?


PAT R&D efforts in manufacturing:

What should constitute acceptable verification of suitability and validation?


Routine manufacturing using PATs:

What should be the regulatory standard for accepting an on-line measurement to replace end product testing?

Level of built-in redundancy?


Identify steps for resolving OOS observations:

Under what conditions can end product testing be used to resolve OOS observations?

Using on-line NIR (for blend, dry, content, dissolution) and HPLC as examples of PAT, please outline the essential experiments (hypothesis or questions) that should be conducted by a company to successfully develop and validate these tools for use in manufacturing operations.


What criteria should be used to ensure that relevant critical formulation/process variables have been identified and appropriate PAT tools selected to ensure their optimal control?

Criteria should be based on

PATs either individually or in aggregate are predictive of final product quality.

What information should be collected to justify use of indirect measurements (e.g. signature or correlations) that relate to product quality/performance attributes?


When and to what extent would FDA involvement facilitate PAT R&D and application projects?