A credible global regulatory strategy is an early-phase imperative, not a late-stage commercial exercise

Asia has surpassed Europe as a center of biopharmaceutical innovation and is on track to rival the United States, with China accounting for a growing share of first-in-class programs.¹ Meanwhile, the commercial logic that has driven drug development for decades is being upended. U.S. free-market pricing offered significantly higher returns than price controls in Europe or Asia, incentivizing companies to prioritize U.S. regulatory approval and launches. Now, for example, the most-favored-nation (MFN) policy is challenging that premium, even though the U.S. remains the largest single market.²   

A credible global regulatory plan is no longer a late-stage commercial exercise; it is an early-phase scientific one. To recoup their investment in a new therapy, sponsors need rapid approval across many markets. Most teams plan locally, focusing on their home regulator and assuming others will follow, which is not always the case. Regulatory differences cause delays and gaps that are costly if addressed late. Missing dose-optimization studies, for instance, can increase costs due to expensive, time-consuming post-marketing requirements. Small dose-finding studies could have prevented delays or a limited label. 

The remedy is to treat the global plan as an early-phase deliverable rather than a downstream filing exercise. An integrated, end-to-end evidence-generation plan—one that anticipates each major region’s regulatory expectations and embeds the answers in first-in-human (FIH) and dose-finding studies—does double duty: it de-risks eventual submissions and, for smaller companies, signals to partners and investors that the program has been thought through to approval.³ Crucially, the work is region-specific; the questions a developer must answer depend on where it is located and where it seeks approval. Three region-specific imperatives follow:

U.S.-based developers: design beyond the FDA

U.S.-based teams tend to assume that the endpoints and trial designs the FDA accepts will satisfy regulators everywhere. They frequently do not due to differences in legislation, policies, and guidelines. In rare and last-line indications especially, there is no global consensus on which surrogate endpoints justify early or accelerated approval, so a study optimized for one agency can leave a gap another will not accept. The same logic governs the real-world evidence that gives a single-arm study its context: design it alongside the trial, because a study assembled after the clinical trial data have read out invites the charge of cherry-picking.

The same blind spot runs the other way. U.S.-based companies that build a dossier largely on non-U.S. data can stall at the FDA, which has turned down programs that enrolled too few U.S. patients, or too little diversity, to support extrapolation to U.S. clinical practice. Where a U.S. launch matters, that requirement should be included in the enrollment plan from the outset, not in a costly bridging study afterward. The ultimate defeat is a complete response letter from the FDA.

The discipline that prevents this is early scientific engagement abroad—pressure-testing endpoint and design assumptions with European and other authorities before pivotal studies are locked, not after. Former agency reviewers are especially valuable here: for instance, they can anticipate where two regulators will diverge on the same endpoint, and help shape a single design that satisfies both.

Europe-based developers: optimize the dose early

European sponsors frequently defer dose optimization, and the regulatory system enables this: the EMA has so far operated on a long-standing principle that clinical pharmacology or suboptimal dose should not, on its own, block approval as long as quality, efficacy, and safety are established and the benefit-risk balance can be considered positive. The FDA no longer affords that latitude and will not hesitate to reject applications based on a dose that was never properly optimized.

Optimizing early is also the more cost-effective path. A small, randomized early-phase dose-comparison study costs a fraction of the post-marketing non-inferiority study that a sponsor would otherwise be required to run by the FDA. For any program that intends to go global, the dose should be optimized to the strictest standard from the outset.

China-based developers and China-bound programs: synchronize early

Increasingly, innovation originates in China. However, data generated in one region does not always transfer to another. The same cancer can have different underlying causes in different parts of the world, viral in one population and lifestyle-related in another. Those differences can change how well a therapy works. A plan that assumes one-to-one extrapolation invites a regulator to restrict the label, or reject the dossier, on a question the sponsor never tested. The fix is not necessarily a new study: an early, rigorous review of etiology and epidemiology can either consolidate the global strategy or flag where additional patients are needed regionally. Framed correctly, that review becomes a formal ethnic-sensitivity analysis under the International Conference on Harmonisation’s Tripartite Guideline E5  (ICH-E5)⁴—weighing Asian against non-Asian and Chinese against non-Chinese populations—which is the evidence regulators use to judge whether foreign data can stand in for local studies.

Where regional sensitivity data are required, an ethno-bridging study in an early-phase unit, enrolling a defined population under a tightly written protocol, can generate that evidence faster than establishing a separate cohort overseas, while keeping the global timeline intact.

Sponsors who align early with the Center for Drug Evaluation (CDE) can substitute foreign data for local studies, or run a China cohort in parallel with a global pivotal trial rather than in sequence, saving the better part of a year on the path to a synchronized filing.

For example, by integrating China into early development, sponsors can benefit from a rapidly maturing regulatory environment that rewards synchronized innovation. 

The China Center for Drug Evaluation (CDE) now offers a 30-working-day (WD) review for Category 1 innovative drug clinical trial applications (CTAs) that are part of globally synchronized development.⁵ This efficiency extends to clinical start-up: studies are initiated (defined as the first Informed Consent Form being signed) within 12 weeks of CTA approval (as part of the requirement in the 30-WD program), compared to the normal duration of 6 months in 2024. Furthermore, early involvement helps maximize the six-year regulatory data protection period, which is otherwise reduced by the "drug lag" between foreign and domestic approvals. 

Conducting early-phase clinical trials in China is a strategic catalyst for accelerating global development programs and streamlining the path to local licensure. Establishing Chinese pharmacokinetic (PK) data during early overseas studies (such as FIH trials) can help waive or reduce the need for standalone bridging trials. Early data confirm PK/PD consistency across populations and address potential risk factors, such as body weight and genetic polymorphisms, that Chinese reviewers prioritize.

Japan applies the same logic through the Pharmaceutical and Medical Devices Agency (PMDA), which has long used ICH-E5 to assess whether foreign data extrapolate to Japanese patients and has historically expected Japanese PK data or bridging data whenever ethnic differences are plausible. Recent guidance has relaxed the reflexive requirement for a standalone Japanese Phase I study before a sponsor joins a global trial, so including Japanese subjects in a multi-regional trial or an early-phase cohort can keep Japan on the same synchronized timeline rather than filing years behind.⁶

Getting to global approval has never mattered more

As emerging markets account for a larger share of the revenue mix and patient populations for targeted therapies grow smaller and more dispersed worldwide, the cost of a local plan compounds. Success comes from building a global view early, knowing the product, the disease, and the regional differences regulators scrutinize, and from executing an integrated plan with the flexibility to adapt as requirements shift.

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References: 

1. The emerging epicenter: Asia’s role in biopharma’s future, McKinsey & Company (January 7, 2026). 
2. Executive Order: Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients, The White House (May 12, 2025).
3. Evidence planning for biotechs: Closing gaps to maximize value, Parexel Blog Post (November 4, 2025). 
4. Ethnic Factors in the Acceptability of Foreign Clinical Data E5 (R1), ICH Harmonised Tripartite Guideline (March 11, 1998).
5. Policy Interpretation of the Announcement on Optimizing of the Review and Approval Process for Clinical Trials of Innovative Drugs, National Medical Products Administration Announcement No. 86 (October 14, 2025).
6. Basic principles for conducting phase 1 studies in Japanese prior to initiating multi-regional clinical trials including Japan for drugs in which early clinical development is preceding outside Japan, PSB/PED Notification No. 1225-2 (December 25, 2023).
     

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