P326: Beyond Harmonization: Visualizing Regulatory Gaps in the Product Lifecycle for Global Simultaneous Submission and Approval
Poster Presenter
Yuki Miyatake
Sr Group Manager
Eli Lilly and Company Japan
Objectives
Global simultaneous development and approval are key to delivering medicines to patients worldwide even earlier. While ICH harmonization has been remarkable, practical difficulties for sponsors remain often misunderstood. We visualize these gaps and propose directions for enhanced convergence.
Method
We compared regulatory systems for NME versus non-NME approvals (new indications, line extensions, new dosage forms) across nine jurisdictions. We also conducted qualitative research with regulatory affairs professionals at Eli Lilly and Company affiliates across multiple countries.
Results
Our analysis revealed that while ICH harmonization has broadly aligned scientific standards, significant regulatory complexity remains across both NME and non-NME pathways from the sponsors’ perspective.
For NME approvals, review timelines are transparently published by authorities directly or through third parties, and continuous efforts have been made to expedite reviews. For example, Japan’s PMDA has achieved among the fastest review times globally, while other authorities have introduced expedited pathways and international collaborative reviews to prioritize important medicines. In contrast, for non-NME approvals, regulatory systems differ fundamentally. The US reviews efficacy supplements (sNDA/sBLA) under a 10-month PDUFA target; the EU assesses new indication variations (Type II) under a 90-day active review timetable, with additional time for sponsors’ responses; and Japan’s PMDA reviews partial change approvals within a 12-month target. PMDA also publishes detailed review reports and discloses the number of non-NME approvals with their approval list, whereas comparable documentation from other authorities is often less accessible.
Furthermore, the practical implementation of ICH guidelines and the emphasis placed during reviews differ across authorities for both NME and non-NME pathways. Even where harmonized guidelines exist, divergences in data expectations and regulatory interpretation add layers of complexity that are not visible from the guidelines themselves.
As a result, sponsors must develop jurisdiction-specific strategies, meaning patients in some regions inevitably face delays in accessing innovative medicines and their expanded therapeutic uses—ultimately limiting improvements in global health.
Conclusion
Delivering innovative medicines to patients worldwide more quickly is vital for advancing global health. ICH guideline harmonization has driven remarkable progress toward this goal, yet our study suggests that challenges remain when sponsors pursue global simultaneous development and approval. Overcoming these challenges requires convergence of regulatory systems and their practical operations.
Each country’s regulatory system reflects its own legal traditions, and full unification is neither realistic nor necessary. However, our research revealed that the submission and approval processes across authorities—particularly for non-NME regulatory processes—differ in their regulatory frameworks, types of information disclosed, and level of detail available to sponsors.
Therefore, we propose three directions: (1) furthering transparency of non-NME regulatory requirements for some regulatory systems, as has been achieved for NMEs, to enable patients and sponsors to better understand the current landscape and to promote regulatory convergence; (2) leveraging international cooperation through reliance models such as Project Orbis to build an environment where reviewers across authorities can facilitate mutual understanding of the regulatory philosophies behind differing guideline implementations; and (3) pursuing convergence of systems and operations beyond harmonization through dialogue among industry, regulators, and academia, informed by enhanced transparency and mutual understanding.
By advancing these three directions step by step, we can move beyond harmonization of regulatory principles to coordination at the level of actual decision-making and operations, thereby moving closer to a regulatory environment that facilitates faster delivery of medicines worldwide—ultimately contributing to improved global health and better outcomes for patients around the world.
