Pediatric · n=21
41 d
71.4% below median
Across 57 Phase III cell therapy EU submissions, the median end-to-end CTIS review was 70 days with an SD of 49.5. Country-specific CTIS Part II decisions were slower and much more dispersed, with a median of 100 days and SD of 264.7 across 172 country observations. Calendar month, pediatric status, randomisation, therapy mix, and national site footprint separated faster from delayed reviews more clearly than total country count or overall site count.
The overall EU submission timeline and the country-specific CTIS Part II timeline should be read separately. End-to-end review runs from initial EU CTIS submission to first authorization; Part II measures each country from its earliest Part II submission to its latest country decision.
Half of EU submissions reached first authorization within 70 days, but the country-level Part II distribution had a pronounced long tail: its mean was 262.7 days despite a 100-day median.
At 60 days, 28 of 57 EU submissions (49.1%) had first authorization, while 77 of 172 country Part II observations (44.8%) had a country decision. By 180 days, end-to-end coverage reached 98.2%, but Part II coverage reached only 54.1%.
The practical end-to-end planning threshold was close to 60–70 days. Country Part II planning required a wider buffer: 79 of 172 observations (45.9%) still exceeded 180 days.
Among countries with at least three observations, the Netherlands had the shortest median Part II duration at 28 days, followed by Finland at 36 days and Poland at 48 days. Austria and Czechia had the longest medians at 464.5 and 441.5 days.
| Country | Observations | Median | SD |
|---|---|---|---|
| Netherlands | 17 | 28 d | 289.5 |
| Finland | 3 | 36 d | 455.9 |
| Romania | 1 | 38 d | — |
| Portugal | 2 | 40.5 d | 26.2 |
| Poland | 9 | 48 d | 204.2 |
| Belgium | 10 | 62.5 d | 283.1 |
| France | 20 | 65.5 d | 268.4 |
| Greece | 5 | 117 d | 222.7 |
| Italy | 22 | 117 d | 250.5 |
| Sweden | 10 | 128.5 d | 300.1 |
| Spain | 19 | 195 d | 251.9 |
| Germany | 25 | 237 d | 276.2 |
| Hungary | 2 | 243 d | 258.8 |
| Denmark | 6 | 249.5 d | 326.6 |
| Norway | 6 | 251 d | 330.7 |
| Slovenia | 1 | 334 d | — |
| Czechia | 6 | 441.5 d | 221.7 |
| Austria | 6 | 464.5 d | 312.9 |
| Bulgaria | 1 | 468 d | — |
| Slovakia | 1 | 582 d | — |
Country medians differed by more than sixteenfold among countries with n≥3. The large SDs in several countries show that national performance was not uniform across submissions, so the country median is more decision-useful than the mean.
“Faster” means below the 70-day end-to-end median. The largest favorable differences appeared in pediatric submissions, non-randomized designs, mixed-modality programs, and combination regimens.
Pediatric submissions had the clearest favorable split: median review was 41 versus 95 days, and 71.4% versus 36.1% were faster than the cohort median. Randomized and cell-therapy-only submissions were substantially less likely to fall below 70 days.
December EU submissions had the strongest calendar-month delay signal: 9 of 11 (81.8%) took at least 60 days and the same share took at least 90 days. Adult, randomized, cell-therapy-only, oncology, and multiple-myeloma submissions also had elevated delay rates.
| Factor group | n | Median | ≥60 d | ≥90 d |
|---|---|---|---|---|
| December EU submissions | 11 | 131 d | 81.8% | 81.8% |
| Non-pediatric trials | 36 | 95 d | 63.9% | 55.6% |
| Randomized designs | 23 | 103 d | 60.9% | 56.5% |
| Cell therapy only | 26 | 95 d | 61.5% | 53.8% |
| Oncology submissions | 16 | 95.5 d | 62.5% | 56.2% |
| Multiple myeloma | 9 | 110 d | 55.6% | 55.6% |
| Disease cluster | n | Median | ≥60 d | ≥90 d |
|---|---|---|---|---|
| Lymphoma or leukaemia | 5 | 70 d | 60.0% | 40.0% |
| Musculoskeletal repair | 3 | 86 d | 66.7% | 33.3% |
| Melanoma | 3 | 91 d | 100.0% | 66.7% |
| Multiple myeloma | 9 | 110 d | 55.6% | 55.6% |
The most actionable risk markers were timing and design-related rather than sheer scale. Multiple myeloma had a 110-day median, while the broader oncology-only group had a 95.5-day median and a 56.3% ≥90-day delay rate.
Yes. The month pattern was visible in both EU end-to-end review and country CTIS Part II, without using year as an analytical variable.
September–November EU submissions had a 27.5-day median, compared with 116 days for January, March and December. At Part II level, February, March and June had a 38-day median, versus 476 days for January, April and October.
At the overall EU submission level, scale showed weak monotonic relationships with end-to-end time. The number of countries had Spearman ρ=0.05, total sites ρ=0.14, and target sample size ρ=0.23. Country Part II site count had a small positive relationship with duration, ρ=0.16.
| Country site footprint | n | Median Part II | ≥60 d | ≥90 d |
|---|---|---|---|---|
| 1–3 sites | 105 | 63 d | 53.3% | 45.7% |
| 4–7 sites | 45 | 302 d | 55.6% | 53.3% |
| 8+ sites | 22 | 504.5 d | 72.7% | 68.2% |
Adding countries or sites did not consistently lengthen overall EU authorization. The sharper operational signal appeared inside Part II: country footprints with 8+ sites had a 504.5-day median and 68.2% exceeded 90 days, versus a 63-day median and 45.7% for 1–3 sites.
The data support a two-layer planning model: use 70 days as the central end-to-end EU CTIS benchmark, but plan national Part II work around a 100-day median and country-specific tail risk.
Portfolio planning should not apply one CTIS duration to every country. The strongest risk-control opportunities are to account for calendar month, national Part II site footprint, randomized oncology design, and cell-therapy-only programs before setting the expected authorization date.
CTIS: Clinical Trials Information System used for EU clinical trial applications.
End to end: Days from initial EU CTIS submission to first authorization. This measure applies to the overall submission, not an individual country.
Part II: Country-specific days from earliest CTIS Part II submission to the latest country decision or authorization recorded in the dataset.
SD: Sample standard deviation. Faster than median: under 70 end-to-end days or under 100 Part II days. Substantial delay: at least 60 or at least 90 days.
Analysis scope: 57 Phase III-designated cell therapy EU submissions, 172 country-specific Part II observations across 20 countries. Calendar year was not used as an explanatory factor.