Study Reveals Persistent Divergence in Global Regulatory Approaches to Expedited Oncology Approvals

Among oncology drugs first approved by the US Food and Drug Administration (FDA) through expedited pathways, other major regulatory authorities frequently diverged in how they approved the same products—both in regulatory frameworks and evidentiary thresholds—according to research published in Frontiers in Pharmacology.

Yeh Hyun Kim, of the College of Pharmacy at Ewha Womans University in Seoul, and colleagues conducted a review of 36 oncology drug-indication pairs granted expedited approval by the FDA between 2019 and 2023, subsequently reviewed by the European Medicines Agency (EMA), Australia's Therapeutic Goods Administration (TGA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA).

"Our findings highlight persistent divergence in regulatory frameworks and evidentiary thresholds across agencies, reflected in differences in data maturity requirements, approval pathways, and review timing that contribute to fragmented regulatory outcomes and unequal patient access," Kim and colleagues wrote.

Divergent Approval Pathways Across Agencies

Overall, EMA authorized 28 drug-indication pairs, TGA authorized 18, and PMDA authorized 15 across expedited or standard pathways. Of these, EMA authorized 20 drug-indication pairs through expedited pathways and 8 through standard pathways. TGA authorized 15 through expedited and 5 through standard pathways. PMDA authorized 14 drug-indication pairs through standard pathways and only 1 through an expedited pathway.

A majority of pivotal trials analyzed across all four agencies were single-arm studies with evidence from early-phase trials involving small patient populations of 200 participants or fewer. Nearly all agencies analyzed the same primary endpoint across pivotal trials.

EMA: Broader Populations, Later Data Cut-Offs

The researchers found that while EMA used expedited pathways at a similar rate to FDA (71%), the European regulator's target populations tended to be broader, and EMA also had later data cut-off dates compared to FDA.

"In expedited contexts, where pivotal trials analyze 200 or fewer patients, these observed features—namely the use of later data cut-offs and broader population definitions—may reflect the EMA's regulatory emphasis on ensuring sufficient evidence maturity and population characterization within the constraints of conditional approval," the researchers explained.

TGA: High Concordance, Longer Timelines

TGA used an expedited pathway most often compared to FDA (72%) and demonstrated similar analytical interpretations for the same pivotal trials. However, TGA showed longer submission lag times for both high concordance (median 324 days) and low concordance (median 626 days) drug-indication pairs.

The researchers noted that these longer submission gaps "may be associated with a sequential submission strategy by design rather than regulatory inefficiency: sponsors await FDA authorization before initiating TGA submission, after which the TGA conducts a targeted assessment leveraging the existing FDA review."

PMDA: Standard Pathways and Japan-Specific Analyses

PMDA primarily relied on standard approval pathways, with a focus on Japan-specific population analyses. Kim and colleagues noted this "aligns with critiques that Japan's conditional approval functions more like a full approval, limiting regulatory flexibility." The differences between PMDA and FDA may stem from structural differences in eligibility criteria.

Submission Lag Times Reflect Strategic Differences

When comparing submission lag times to FDA, EMA had shorter submission lags for drug-indication pairs with greater concordance with FDA (median 27 days), but substantially more lag time for pairs with low concordance (median 521 days). PMDA mainly had longer submission lag times for drug-indication pairs with low concordance with FDA (median 367 days).

Call for Global Regulatory Harmonization

The researchers emphasized that divergence between regulators on acceptable evidence for expedited approval may conflict with societal expectations for evidentiary certainty versus faster access to products.

"Greater transparency, aligned evidentiary standards, and strengthened international collaboration will be critical to realizing the full potential of expedited programs and promoting global regulatory harmonization," the researchers concluded.

Separately, a study by Allan Cramer and colleagues published in the British Journal of Clinical Pharmacology found that EMA and FDA make highly aligned oncology drug approval decisions, with over 90% agreement in final approval decisions for both new cancer drugs and extensions of indication. That study noted FDA decisions are quicker, with a median of 216 days for new drugs compared to 424 days at the EMA, and 176 days versus 295 days for extensions—though the times between submission and decision did not meaningfully influence the final outcome.