FDA adopts ICH Q12

The US Food and Drug Administration (FDA) adopted the final ICH Q12 Guideline for post-approval change management. The guideline is intended to complement the existing ICH Q8 to Q11 Guidelines, and is composed of a Core Guideline and two Annexes.

Currently, ICH Q12 is in the implementation phase across the ICH regions. However, especially in the EU, revision of local regulations (i.e. the EU Variations Regulation) will have to be performed to fully implement the concepts of Q12 (e.g.: the PACMP can currently be used in the US and in the EU, whereas ECs are not yet used in the EU).

ICH Q12 Core Guideline

In order to ensure a standardized approach, the guidance defines the categorization of Post-Approval CMC (chemistry, manufacturing, and controls) changes, Established Conditions (ECs), Post-Approval Change Management Protocols (PACMPs), and Product Lifecycle Management (PLCM) concepts. In particular, the guideline emphasizes the relationship between Regulatory Assessment and GMP Inspection. Furthermore, the guideline describes how ECs are identified as well as what information can be designated as supportive Information that would not require a regulatory submission, if changed.

ICH Q12 Annexes

The examples provided in the ICH Q12 Annexes are mock examples provided for illustrative purposes. They suggest how the ICH Q12 tools could be applied. In addition, the reporting categories are described. However, they may differ across the ICH regions depending on regional legislation.

Annex I contains illustrative examples for

• ECs for the Manufacturing Process with acceptable ranges and reporting categories (Chemical and  Biological Medicinal Product)
• ECs for Analytical Procedures
• PACMPs
• PLCM Documents

ANNEX II provides a structured approach to analytical procedure changes. 

In addition, the Annex includes a table explaining the terminology for the reporting categories used in the examples:

Packaging Changes

The FDA recently issued a new guidance with recommendations for the appropriate reporting category and the content of post approval change submissions for some common changes to container closure systems (CCS) consisting of glass vials and stoppers used for parenteral drug products (e.g. COVID-19 vaccines).

FDA ICH Q12 implementation

More information on ICH Q12 can be found in the two FDA documents Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Guidance for Industry and Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Annex. In addition, the agency recently issued a draft guidance to help manufacturers implement ICH Q12 by explaining how to submit ECs.