5/6 October 2023
In the October 6, 2015, Federal Register, the FDA announced that they are reopening the comment period for the "Established Conditions: Reportable Chemistry, Manufacturing, and Controls ("CMC") Changes for Approved Drug and Biologic Products; Draft Guidance for Industry." Comments are now due January 4, 2016. The FDA is reopening the comment period for additional 90 days to allow interested persons more time to submit comments on these important issues.
The FDA guidance documents, such as "CMC Post-approval Manufacturing Changes To Be Documented in Annual Reports" intend to clarify the recommended reporting mechanism (i.e., supplement, annual report) for post-approval CMC changes.
The present draft guidance document identifies "those sections of a CTD-formatted application that typically contain information that FDA considers to meet the definition of established conditions".
It is expected that a better understanding of "established conditions" will allow for more effective post-approval change management strategies e.g. by the use of risk management principles (ICH Q9), and knowledge management (ICH Q10). Additionally, this will also provide more regulatory flexibility. In future, an applicant could probably rely upon a robust Pharmaceutical Quality System (PQS) to handle post -approval changes appropriately, resulting in a reduction (or elemination) of certain reporting requirements.
What are "established conditions" for manufacturing and control?
This is a highly discussed topic in context of the planned new ICH Q12 Guideline "Lifecycle Management". The FDA defines established conditions as "the description of the product, manufacturing process, facilities and equipment, and elements of the associated control strategy, as defined in an application, that assure process performance and quality of an approved product. Changes to the established conditions must be reported to the FDA".
An example given in the draft guidance document is:
"if on-line, real-time attribute monitoring is implemented post-approval for a particular unit operation, it may be acceptable to designate the on-line monitoring (e.g., NIR analysis) as an established condition, while removing the inputs and process parameters for the unit operation from the established conditions".