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ICH published a Final Concept Paper for a new ICH Q12 Guideline

  • 25 February 2015
  • change management, chemistry, CMC, continual improvement, control, ICH Q12, knowledge management, lifecycle management, management of post-approval CMC changes, manufacturing, prospective change management,

ASE Pharma Solutions

Recently, ICH published a Final Concept Paper for a new ICH Q12 Guideline entitled “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management”.

There is currently a lack of a harmonised approach on technical and regulatory considerations for product lifecycle management. While the concepts in ICH Q8, Q9, Q10 and Q11 provide opportunities for a more science and risk-based approach for assessing changes across the lifecycle, several gaps exist which limit full realisation of intended benefits. The envisioned post-approval “operational flexibility” has not been achieved. The main emphasis at ICH to date has focused on early stages of the product lifecycle, particularly development and launch.

A similar focus is now needed for the commercial manufacturing phase in order to fill the gaps in the implementation and fully realize the opportunities promised by ICH Q8 to Q11.




ICH Q12 Guideline is intended to work with ICH Q8 to Q11 Guidelines and will provide a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls (CMC) changes in a more predictable and efficient manner across the product lifecycle. Adoption of this guideline will promote innovation and continual improvement, and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain adjustments. It will allow regulators (assessors and inspectors) to better understand, and have more confidence and trust in a firm’s Pharmaceutical Quality System (PQS) for management of post-approval CMC changes. Particularly, the new guideline will implement the lifecycle management of pharmaceutical product through:

  • Regulatory Dossier

o   Explore the development of a harmonised approach to “regulatory commitments” for inclusion in the guideline. Such approaches could enable post approval changes that facilitate continual improvement and encourage the adoption of innovative technologies such as Process Analytical Technology (PAT) and continuous manufacturing.

o   Delineate the appropriate level of detail and information necessary for regulatory assessment and inspection in the dossier, in order to create a more enabling post approval change management system.

  • Pharmaceutical Quality System aspects (ICH Q10)

o   Establish criteria for a harmonised risk-based change management system based on product, process and/or clinical knowledge that effectively evaluates the impact of change on quality, and, as applicable to safety and efficacy.

o   Clarify expectations and reinforce the need to maintain a knowledge management system that ensures continuity of product and process information over the product lifecycle.

  • Post-Approval Change Management Plans and Protocols

o   Introduce the concept of a post-approval management plan that can be used to proactively identify post-approval changes and the mechanism to submit and assess these changes by regulatory authorities (Assessors and Inspectors).

o   Establish criteria for post-approval change management protocols that can be adopted by the ICH regions (enabling a harmonised proactive approach for lifecycle management).

o   Encourage enhanced product development and control strategy approaches (Quality by Design (QbD)) providing opportunities for scientific and risk based foundations for post-approval change management plans.


It is envisaged that the development and implementation of this new guideline would deliver a number of benefits for industry, the regulatory authorities and patients:

  • Harmonise change management, leading to better availability and reliability of the supply by enabling companies and regulators to manage CMC changes in a more transparent and efficient manner across the product lifecycle
  • Facilitate risk-based regulatory oversight and optimisation of resources for assessment and inspection
  • Assist industry in maintaining and updating the dossier to ensure conformance using simplified and harmonised approaches and interpretations of expectations across the ICH regions
  • Emphasize use of the control strategy as a key component of the regulatory commitment in the dossier linking the active dossier with potential future changes
  • Enhance use of regulatory tools for prospective change management (e.g. Post-Approval Change Management (PACM) plans, PACM protocols/comparability protocols, application form)
  • Help assure supply reliability by enabling strategic management of post-approval changes which could mitigate drug shortages related to manufacturing and quality issues
  • Support continual improvement of the manufacturing process and the control strategy which can result in decreased product variability and increased manufacturing efficiency
  • Facilitate the introduction of innovations and PACM
  • Support implementation of the process validation lifecycle concept
  • Enable control strategy lifecycle (e.g., model maintenance, analytical lifecycle)

It is envisaged that this new document will be adopted in 2Q 2017.