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Getting a product approved in one region is hard enough. Getting it approved across the US, Europe, and Japan (ideally within months of each other) requires strategic planning, relationship-building with regulators, and cultural fluency that most development teams underestimate until they’re in the middle of it.
The three major ICH regulators share the same goal of bringing safe, effective products to patients. But they operate through very different lenses, ask fundamentally different questions, and interpret the same data differently.
Sponsors who assume that a technically harmonized dossier equals regulatory alignment across regions are setting themselves up for misalignment, rework, and delays.
Our Nick Capman recently sat down with AJ Acker, Senior Vice President of Regulatory, Quality & Clinical Safety at Annexon Biosciences, to walk through practical strategies for navigating global filings with the FDA, EMA, and PMDA.
AJ brings about 30 years of experience in pharma with a deep focus on rare diseases. He has led global regulatory programs that secured approvals across all three ICH regions and has direct experience negotiating with the FDA, EMA, and PMDA.
Prior to Annexon, AJ served as Senior Vice President of Global Regulatory Affairs at Zogenix (where he also served as President of Zogenix Japan K.K.), and held regulatory leadership roles at Bioskin, Santen, and BioMarin, building a career defined by rare disease programs and multi-regional regulatory strategy.
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AJ’s key insights and practical takeaways
If you’re short on time, here are the most important lessons from the discussion.
FDA, EMA, and PMDA share the same goal but ask fundamentally different questions. AJ frames it simply: The FDA asks, “Does this work and can patients get it quickly?” EMA asks, “Is this meaningfully better than what we already have?” And PMDA asks, “Can this truly be developed and sustained for Japanese patients?” These different lenses show up everywhere: from orphan designations (FDA is the most flexible with early decisions and limited data sets; EMA requires potential significant benefit over existing therapies and reassesses orphan status during approval; Japan requires a credible development plan just to qualify) to clinical data requirements (FDA and EMA accept global data sets more readily, while Japan still typically requires local Japanese data, despite recent guidances adding flexibility).
ICH harmonization provides a common scientific foundation, not regulatory alignment. The ICH has aligned scientific and technical standards across the three regions, reducing redundant studies, standardizing dossier formats, and enabling multi-regional clinical trials. But a fully ICH-compliant program may still face divergent regulatory questions, different post-marketing obligations, and varying approval pathways across regions. Technical alignment and regulatory alignment are not the same thing. Sponsors who treat ICH compliance as a substitute for region-specific regulatory engagement are making one of the most common pitfalls in global development.
Start planning for all three regions early (especially Japan). Late engagement with any region creates misalignment that leads to rework and delayed approvals. This is especially true for Japan. PMDA will specifically ask sponsors why Japan was or was not included in early development, and they consider that question as part of the submission package. Early engagement also unlocks accelerated pathways: orphan designations, accelerated and conditional approval mechanisms, and alignment on endpoints. If you’re considering accelerated approval by the FDA based on a surrogate endpoint, you need to discuss that endpoint with EMA and PMDA to determine whether it’s clinically meaningful in their regions and whether it can support approval there.
Expect different regulators to want different primary endpoints from the same data. AJ shared an example from a pivotal program where FDA and EMA each wanted a different primary endpoint for the same study. The solution: the protocol listed the FDA’s preferred endpoint as the primary and the EMA’s preferred endpoint as the first key secondary, with different statistical analysis plans between regions. That approach required early conversations with both agencies to gain alignment before the study design was locked. Without those conversations, the study could have been designed in a way that satisfied one regulator but not the other.
Japan’s regulatory landscape is changing, but the bar remains high. Japan has historically required Japanese clinical or bridging data, even for rare diseases. Recent guidances have added flexibility, including pathways for approval without Japanese data and conditional approval mechanisms. But AJ notes the bar is still quite high: he’s only aware of two products that have gone through approval without Japanese data, and two that have used the conditional approval pathway. The opportunity is real, but sponsors need to engage PMDA early to understand whether their program qualifies. The regulatory space in Japan is actively evolving, and sponsors who plan prospectively for Japan rather than treating it as an afterthought have a significant advantage.
Local regulatory experts are essential and should be used strategically. Local experts and consultants play a decisive role in bridging the gap between a globally aligned data package and region-specific regulatory expectations. Their value isn’t in producing more data; it’s in shaping the credibility, timing, and interpretability of data at the regional level. They also serve as early warning systems, identifying where a global trial design might clash with regional norms, where an endpoint might be challenged, or where post-marketing commitments might diverge. AJ also recommends using ex-regulators as higher-level strategic advisors rather than day-to-day consultants — they’ve seen many approaches to success and can help navigate challenges like maintaining orphan designation in the EU.
Simultaneous or closely timed filings are becoming the norm, but resource planning is critical. Sequential region-by-region submissions are no longer the default, especially for orphan and accelerated programs. AJ has filed with the FDA and EMA on the exact same day. But simultaneous filings create a significant resource burden: FDA sends responses on a rolling basis, EMA and PMDA have more structured question timelines, and inspections from all three regions can overlap. Sponsors need to align with their commercial teams on launch sequencing (which often influences filing order) and make sure the organization is resourced to handle parallel review cycles. Filing strategy should also account for the asset’s maturity, disease context, data robustness, and whether Japan was planned for early enough.
Plan for questions before you get them. No program gets through a clean review without questions. Sponsors know their data best and should know where the gaps are, where results aren’t entirely clear, and where regulators are likely to push. AJ’s advice: start planning responses to anticipated questions before submissions go out. Have a response team identified and ready. Get internal alignment on trade-offs for post-marketing commitments, conditional approval requirements, and other obligations that may vary by region. The preparation that starts early in development (not at submission) is what determines how smoothly the review process goes.
Building trust with regulators is a long game that pays off at the critical moment. The trusting relationship you build with regulators throughout development is what matters most during the review and approval process. If you’ve built that relationship, they’ll take more time to work with you and listen more carefully. Communication style matters: EMA is more direct and expects transparency; PMDA is less direct, especially in person, and wants to understand the “why” behind decisions; FDA is the most flexible in terms of communication format. AJ also stressed the importance of building relationships with key opinion leaders in the disease area. Regulators will check what sponsors say against KOL perspectives, so alignment in tone and substance across both channels strengthens the submission.
AI is becoming a strategic tool for sharpening submissions. AJ shared a concrete example: before filing with EMA, his team used AI to review their clinical summary against five specific strategic points they wanted to make. AI identified that four of five points were clearly supported by data, but the fifth was backed mostly by hypotheticals rather than actual evidence. The team went back and added data to support that point, something that likely wouldn’t have been caught as easily through traditional review. He also noted that regulators are starting to use AI themselves, which means sponsors should begin thinking about how their documents and questions will be processed by AI tools on the regulatory side.
The future may be a “living dossier.” Looking ahead, AJ expects FDA, EMA, and PMDA to continue harmonizing standards and data formats, but regulatory judgment and lifecycle management obligations will remain distinct. He sees the traditional dossier model evolving: as real-world data registries and long-term follow-up become more integrated into development programs, the line between a development dossier and a lifecycle management dossier may blur. Approval might happen in the middle of a continuous, living submission rather than at the end of a discrete filing process.
One thing to bring back to your team
Look at your current global development strategy and ask whether you’re treating ICH compliance as regulatory alignment (because they’re not the same thing). Consider:
Have you engaged all three regions early enough, or is Japan being treated as an afterthought?
Do you know whether FDA, EMA, and PMDA would accept the same primary endpoint, or are you assuming alignment that hasn’t been tested?
Are you using local regulatory experts and ex-regulators strategically (for credibility, timing, and early warnings) or just for document production?
Have you started planning responses to the questions you know regulators will ask, before submissions go out?
Is your organization resourced to handle parallel review cycles across three regions simultaneously?
The companies that achieve tight global filing timelines are the ones that planned for regional differences from the beginning, engaged regulators early and often, and built the relationships and internal readiness to move through review without losing months to avoidable misalignment.
AJ Acker is Senior Vice President of Regulatory, Quality & Clinical Safety at Annexon Biosciences, where he leads regulatory strategy for the company’s rare disease programs. He has about 30 years of experience in the pharmaceutical industry with a sustained focus on rare diseases and global regulatory approvals across the FDA, EMA, and PMDA.
Prior to Annexon, AJ served as Senior Vice President of Global Regulatory Affairs at Zogenix, where he also served as President of Zogenix Japan K.K. and led successful NDA, MAA, and Japan NDA filings and approvals. He has held regulatory leadership roles at Bioskin, Santen, and BioMarin. AJ is an Oregon State University alumnus based in Napa, California.
Connect with AJ on LinkedIn here.
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