The International Council for Harmonisation (ICH) is signaling a significant shift in how global regulatory guidelines address cell and gene therapies, reflecting the growing complexity and rapid evolution of these advanced products. The ICH Cell and Gene Therapy Discussion Group (CGTDG) has released a discussion paper recommending a more tailored, risk-based approach to regulation that better reflects the unique scientific and manufacturing characteristics of cell and gene therapy products compared to traditional pharmaceuticals.
The effort marks an important step toward greater global alignment as regulators and developers grapple with increasingly divergent regional requirements for advanced therapy medicinal products (ATMPs).
Growing Fragmentation in ATMP Guidance
As part of its analysis, the CGTDG identified more than 300 region-specific ATMP-related guidelines that have been issued in draft or final form by ICH members and observers. This proliferation of localized guidance underscores the challenges sponsors face when developing cell and gene therapies intended for global markets.
According to the group, the expanding patchwork of requirements highlights the need for more harmonized approaches to development, evidence generation, and regulatory assessment across regions. Without greater alignment, sponsors may face duplicated studies, inconsistent expectations, and delayed patient access.
Review of Existing ICH Frameworks
To inform its recommendations, the CGTDG reviewed existing ICH guidelines across quality, safety, efficacy, and multidisciplinary domains, including guidelines currently under revision. The group assessed where existing frameworks adequately support ATMP development and where they fall short due to the inherent complexity, variability, and novelty of cell and gene therapies.
The discussion paper includes a structured overview of priority topics and proposes how these areas could be integrated into the ICH guideline framework moving forward.
Proposed Updates to Key ICH Guidelines
One major recommendation is the development of an annex to ICH Q5E, which addresses comparability assessments for biological products. While Q5E is well suited for well-characterized biologics, the CGTDG concluded that its principles are difficult to apply strictly to ATMPs. The group recommends a broader, risk-based approach that considers the totality of evidence to manage uncertainty and product-specific variability.
The CGTDG also proposed creating an annex to ICH Q11, which focuses on starting materials. This annex would provide ATMP-specific guidance on process development and validation, recognizing the critical role that starting materials play in the safety and consistency of cell and gene therapies.
In addition, the group recommended the development of a new ICH safety guideline dedicated to the nonclinical evaluation of ATMPs. Proposed topics include species selection, study duration, endpoint selection, and assessment of risks such as carcinogenicity, tumorigenicity, and germline transmission.
Implications for Developers
If adopted, these changes could significantly influence global development strategies for cell and gene therapies. A more harmonized and risk-based ICH framework may help reduce regional inconsistencies while setting clearer expectations for regulators and sponsors alike.
For developers, the proposals highlight the importance of early regulatory strategy, thoughtful evidence planning, and global alignment when advancing ATMP programs.
How EMMA International Supports Cell and Gene Therapy Developers
At EMMA International, we support cell and gene therapy developers with global regulatory strategy, ATMP classification, comparability planning, nonclinical strategy, and lifecycle management across FDA, EMA, and international markets. Our teams help sponsors navigate evolving ICH expectations while maintaining compliance and development momentum.
Contact EMMA International at 248-987-4497 or email info@emmainternational.com to learn more.
Sources
International Council for Harmonisation. Cell and Gene Therapy Discussion Group discussion paper on advancing ICH guidance for ATMPs. December 2025.
Regulatory Affairs Professionals Society. ICH looks to revamp its guidelines on cell and gene therapies. December 15, 2025.
International Council for Harmonisation. ICH Q5E and Q11 guidelines.
