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Country-specific requirements and maintaining documents containing different quality information for the same product have always been challenging. Excessive inventory segregation, the likelihood of manufacturing and Regulatory compliance errors, and varying submission, evaluation, and deployment deadlines all add to the complexity of product supply chain regulation worldwide. As a result, various legal frameworks around the globe are focusing on implementing innovative modifications or enhancements to increase process efficiency and robustness.
The ICH Q12 guideline: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management offers unique tools for streamlining and integrating post-approval Chemistry, Manufacturing, and Controls (CMC) changes. The tools, in collaboration with ICH guidelines Q8, Q9, Q10, and Q11, will assist in creating a more advanced Quality-by-Design (QbD) framework for post-approval submissions. As per the QbD concept, quality cannot be tested on the product, but it should be built into it, allowing continuous implementation of changes without delay.
Worldwide Implementation Scenario of ICH Q12
With the understanding to minimize the risk of drug inadequacy while ensuring high standards of quality, safety, and efficacy of the drugs, many markets have adopted the ICH Q12. Let’s see the extent to which some of the largest markets in the world, like Europe, the US, Japan, and Canada, are managing the post-approval changes.
US FDA
The final ICH Q12 guideline and annexes published on the US FDA's website in May 2021 describe recommendations on identifying, submitting, and establishing the suggested Established Conditions (ECs). It also clarifies the relationship between ICH Q12 Post-Approval Change Management Protocols (PACMPs) and Food and Drug Administration (FDA) comparability protocols. It describes translating ICH Q12 post-approval change reporting aspects to the existing FDA supplement categories and offers specific examples of how to use a Product Life Cycle Management (PLCM) document.
EMA
The European Medicines Agency (EMA) was the first global Health Authority to employ ICH Q12 in January 2020, with implementation guidance authorized in March 2020. Following substantial discussions and negotiations during ICH Q12 drafting and approval, differences between certain concepts in ICH Q12 and the existing EU legislative system could not be completely resolved, restricting ICH Q12 from becoming fully integrated into the EU. The EMA's implementation guideline highlights that "the Regulatory framework invariably supersedes over scientific and technical regulations," which states that the requirements outlined in the current EU Variations Regulation and associated EU Variations Guidelines must always be followed. The European Commission recently announced that it has begun the process of revising the EU's pharmaceutical legislation, issuing a "combined evaluation roadmap/inception impact assessment."
PMDA
The Pharmaceutical and Medical Devices Agency (PMDA) in Japan has adopted an internal working group to facilitate the implementation of ICH Q12. One of the intriguing aspects that must be addressed is the relationship and potential for alignment between the Japanese Module 1 Application Form, which contains the "approved matters," and the ICH Q12 concepts of ECs with associated reporting categories and the PLCM document. In terms of PACMPs, there is currently no comparable concept in Japan, so a change in national regulations will be required to implement it.
Health Canada
Health Canada, in the second half of 2021, targeted implementing ICH Q12 to "allow sufficient time for regulators and stakeholders to prepare." To that end, Health Canada intended to launch stakeholder consultations in 2021 to gather feedback on the final elements of Q12 implementation in Canada. Similarly, there are some possibilities in Japan for alignment of the Canadian CPID with the ICH Q12 concepts of ECs and the PLCM document, as well as more widespread acceptance of PACMPs.
As individual companies started to adopt ECs and ICH Q12 concepts, it became clear that there was some disconnect in approaches and associated terminology addressed to Health Authorities. Recent engagements between industry leaders and Health Authorities have highlighted key issues faced by regulators and sponsors in implementing ICH Q12, as well as a potential future path to a more harmonized approach to post-approval change management.
Country | Health Authority | Status | Considerations |
The United States of America | USFDA | Implemented | Overall, the concept of EC is consistent with FDA regulations in 21 CFR 71 314.70(a)(1)(i), 314.97(a), and 601.12(a)(1). |
Europe | EMA | In the process of implementation | Certain ICH Q12 elements such as ECs and PLCM documents are not compatible with the current legal framework. Recently announced EU legislation revision initiative may change this and enable the use of all ICH Q12 tools. |
Japan | PMDA | Implemented | The EC and PLCM documents must be aligned with the Japanese Application Form. PACMP is a novel concept that requires the revision of the existing legal framework (ongoing). |
Canada | Health Canada | In the process of Implementation | EC and PLCM will need to be aligned with the Canadian Certified Product Information Document (CPID). There has been limited experience with PACMPs so far. |
Worldwide adoption of ICH Q12 tools can provide a consistent approach to PLCM, with the potential for application in non-ICH countries as well. A Regulatory partner can assist in divulging the harmonized approach to post-approval change management described in ICH Q12. This will "profit patients, manufacturers, and Regulatory authorities by promoting innovation and quality improvement in the pharmaceutical sector, reinforcing quality checks, and increasing the availability of medicinal products." Contact Freyr for more.
