Globalisation of the supply chain and market for medicinal products has resulted in a growing number of different procedures, rules and regulations which Marketing Authorization (MA) Holders must follow whenever changes to chemistry, manufacturing and controls (CMC) are required. The ICH Q12 guideline provides a globally agreed framework to facilitate the management of post-approval CMC changes. The ICH Q12 guideline is built on the framework of ICH Q8, Q9, Q10 and Q11 to support science and risk-based approaches to managing changes during commercial manufacturing.

ICH Q12 will give a thorough understanding of the Pharmaceutical Quality systems (PQS) for managing post-approval CMC changes and the potential regulatory advantage for certain post-approval changes. It allows the manufacturer to determine established conditions and efficiently manage post-approval changes through risk management. It is also intended to demonstrate how increased product and process knowledge can reduce the number of regulatory submissions, which will consequently reduce regulatory oversight prior to implementation.

The guideline is intended to promote innovation and continual improvement and thus strengthen quality assurance and the reliable supply of products, including proactive planning of supply chain adjustments, all of which will benefit patients, industry and regulatory authorities.

The EMA published the ICH Q12 Step 5 Guideline and its annexes in full on March 4, 2020. This guideline applies to pharmaceutical drug substances and products (both chemical and biological) requiring a MA; and to drug-device combination products that meet the definition of a pharmaceutical or biological product.

Key principles of ICH Q12 include:
  • Management of post-approval CMC changes in a predictable and efficient manner
  • Regulatory tools and enablers (e.g., Established Conditions (ECs), Product Lifecycle Management (PLCM) Document, Post-Approval Change Management Protocol (PACMP)) with associated guiding principles
  • Demonstration of how increased product and process knowledge contributes to precise and accurate understanding of which post-approval changes require regulatory submission
  • The importance of an effective pharmaceutical quality system (PQS) in the management of changes and the relationship between Regulatory Assessment and Inspection
  • Structured approaches for frequent CMC Post-Approval Changes and Stability Data Approaches to support the evaluation of CMC Changes.
Our expertise at ProductLife Group enables manufacturers to successfully comply with the ICH Q12 guidelines. We provide tactical and strategic support in the following areas:
  • Risk-based Categorisation
Help in the risk-based categorisation and submission strategy of Post-Approval CMC Changes, including high risk changes requiring prior approval from the Competent Authority (CA), moderate and low risk changes requiring notification to the CA and changes not required to be reported and which are managed and documented within the PQS, but may be verified during routine or other inspection.
  • Established Conditions for Manufacturing and Control
Creating a harmonised approach to defining the elements considered necessary to assure product quality and which would trigger a regulatory submission if changed post-approval.
  • Submission Planning
Help in the planning, format, preparation and submission of the PLCM and PACMP documents to summarise, facilitate and benefit post-approval changes.
  • Gap Analysis
Overview, review, evaluation and gap analysis of the PQS in compliance with ICH Q10 and regional GMP requirements where the application is filed.
  • Acting Intermediary
ProductLife Group can act as an intermediary to facilitate effective communication between regulatory assessors and inspectors, to allow oversight of product lifecycle management.
  • Advice on lower risk changes
Giving advice on the suitability of a structured approach for frequent CMC changes of a lower risk allowing the change to be made with immediate or other post-implementation notification, as these changes do not require prior approval by a CA.
  • Post-approval stability study strategy
Planning of the scope and design of post-approval stability studies informed by the knowledge and experience acquired since product authorization. The approaches could be included in a PACMP and will be appropriately justified.   Our team are on hand to provide assistance and to ensure compliance with the ICH Q12. Contact us to find out more.
← Back to all