FDA facilitates the management of post approval CMC to harmonize regulatory approval of drugs with ICH Q12 guideline.

This guidance applies to pharmaceutical drug substances and products (both chemical and biological) that require a marketing authorization and to drug-device combination products that meet the definition of a pharmaceutical or biological product. 

Regulatory tools and Enablers

Following are the regulatory tools and enablers associated with the guideline:

Categorization of Post approval CMC Changes (section II)—

Describes a framework that encompasses a risk-based categorization for the type of communication expected of the Marketing Authorization Holder (MAH) with the regulatory authority regarding CMC changes.

Established Conditions (section III)—

The concept of Established Conditions (ECs) provides a clear understanding between the MAH and regulatory authorities regarding the elements to assure product quality and that involve a regulatory communication, if changed. This section describes how ECs are identified as well as what information can be designated as supportive information that would not involve a regulatory communication, if changed. In addition, guidance is included for managing revisions to ECs.

Post approval Change Management Protocol (section IV)—

The Post approval Change Management Protocol (PACMP) is a regulatory tool that provides predictability regarding the information required to support a CMC change and the type of regulatory submission based on prior agreement between the MAH and regulatory authority. Such a mechanism enables planning and implementation of future changes to ECs in an efficient and predictable manner.

Product Lifecycle Management Document (section V)—

The Product Lifecycle Management (PLCM) document serves as a central repository for ECs and the associated reporting category for changes made to ECs. The document also captures how a product will be managed during the commercial phase of the lifecycle, including relevant post approval CMC commitments and PACMPs.

Pharmaceutical Quality System and Change Management (section VI)—

An effective PQS as described in ICH Q10 and compliance with regional good manufacturing practices (GMPs) are necessary to gain full benefit from this guidance. Management of manufacturing changes across the supply chain is an essential part of an effective change management system. This guidance provides recommendations for robust change management across single or multiple entities involved in the manufacture of a pharmaceutical product.

Relationship Between Regulatory Assessment and Inspection (section VII)—

This section outlines the complementary roles of regulatory assessment and inspection in the oversight of post approval changes and how communication between assessors and inspectors facilitates the use of the tools included herein.

Structured Approaches for Frequent CMC Post approval Changes (section VIII)—

In addition to other tools described above, this section describes a strategy for a structured approach applicable to frequent CMC changes and a discussion of data expectations to enable the use of immediate or other post-implementation notification.

Stability Data Approaches to Support the Evaluation of CMC Changes (section IX)—

This section provides additional science- and risk-based approaches that are relevant to strategies for confirmatory stability studies to enable timelier implementation of CMC changes.

About Global Regulatory Partners

Global Regulatory Partners Inc, (GRP) is an American company that provides regulatory affairs, clinical, quality and safety services to medical devices, pharmaceutical, cosmetic and Food Supplement companies globally.

GRP headquarters is located in Massachusetts USA and its main affiliates are located in China, Japan, Brazil, and Mexico. GRP helps many life science companies register their products in different countries in compliance with local regulations. 

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