Across 153 European Phase I cell therapy trials, the median CTIS end to end review interval was 77 days with an SD of 50.5 days. Country-specific CTIS Part II intervals were materially longer and more variable, with a median of 189 days and an SD of 233.7 days across 205 country observations. Faster outcomes clustered around October submissions, orphan-designated studies and submissions involving two to three countries, while December submissions, first-in-human studies, four or more countries and larger country site networks were associated with delay.
The observed CTIS end to end interval—from initial EU submission to first authorization—had a median of 77 days and SD of 50.5 days. The country-specific Part II interval—from the earliest national Part II submission to the latest national decision or authorization—had a median of 189 days and SD of 233.7 days. These are separate measures and are not additive.
The country-specific Part II measure was 112 days longer at the median and showed more than four times the dispersion by SD. Country execution—not the shared end to end authorization alone—therefore produced the widest timing uncertainty in this Phase I cell therapy cohort.
For end to end CTIS review, 56 of 153 trials (36.6%) were authorized within 30 days, 72 (47.1%) within 60 days and 87 (56.9%) within 90 days. For country Part II, 49 of 205 observations (23.9%) completed within 30 days, 71 (34.6%) within 60 days and 86 (42.0%) within 90 days.
| Interval | End to end | Trials | Part II | Country records |
|---|---|---|---|---|
| ≤30 days | 36.6% | 56/153 | 23.9% | 49/205 |
| ≤60 days | 47.1% | 72/153 | 34.6% | 71/205 |
| ≤90 days | 56.9% | 87/153 | 42.0% | 86/205 |
| ≤120 days | 83.7% | 128/153 | 45.9% | 94/205 |
| ≤180 days | 98.0% | 150/153 | 48.8% | 100/205 |
| ≤240 days | 100.0% | 153/153 | 56.6% | 116/205 |
| ≤365 days | 100.0% | 153/153 | 71.2% | 146/205 |
The 77-day end to end median sits between the 60- and 90-day planning windows: fewer than half of trials cleared by day 60, but 83.7% cleared by day 120. Country Part II crossed 50% only after 180 days, reaching 56.6% by day 240 and 71.2% by one year.
Among countries with at least 10 Part II observations, Spain had the shortest median at 115 days, followed by Italy at 204 days, the Netherlands at 225 days, France at 240.5 days, Germany at 248 days and Belgium at 282 days. The full table reports median and SD for every country represented.
| Country | n | Median days | SD days |
|---|---|---|---|
| Austria | 2 | 25 | 5.7 |
| Slovenia | 1 | 27 | — |
| Hungary | 1 | 40 | — |
| Romania | 1 | 65 | — |
| Czechia | 3 | 75 | 76.4 |
| Denmark | 7 | 78 | 180.1 |
| Norway | 2 | 106 | 137.2 |
| Spain | 47 | 115 | 240.1 |
| Poland | 8 | 150 | 226.5 |
| Italy | 23 | 204 | 241.1 |
| Netherlands | 17 | 225 | 225.7 |
| Luxembourg | 1 | 231 | — |
| France | 34 | 240.5 | 226.5 |
| Germany | 39 | 248 | 250.2 |
| Belgium | 10 | 282 | 325.1 |
| Greece | 2 | 298.5 | 211.4 |
| Sweden | 7 | 329 | 196.5 |
Country selection materially changes the expected Part II schedule. Among higher-volume countries, Spain’s median was 133 days shorter than Germany’s and 167 days shorter than Belgium’s, while high SDs show that country medians should be used with contingency buffers rather than as fixed deadlines.
October submissions had a 31-day median and 18 of 23 trials (78.3%) finished below the overall 77-day median. December submissions had a 112-day median; only 3 of 20 (15.0%) were below median and 16 of 20 (80.0%) took at least 90 days. June was also favorable at 33 days, while May and November had medians of 104 and 93 days.
| Month | n | Median | Below 77d | ≥90d |
|---|---|---|---|---|
| January | 15 | 22 | 60.0% | 33.3% |
| February | 3 | 105 | 0.0% | 66.7% |
| March | 3 | 111 | 0.0% | 100.0% |
| April | 9 | 50 | 55.6% | 44.4% |
| May | 7 | 104 | 14.3% | 85.7% |
| June | 15 | 33 | 73.3% | 26.7% |
| July | 16 | 75 | 50.0% | 50.0% |
| August | 17 | 27 | 58.8% | 35.3% |
| September | 13 | 52 | 61.5% | 30.8% |
| October | 23 | 31 | 78.3% | 13.0% |
| November | 12 | 93 | 25.0% | 50.0% |
| December | 20 | 112 | 15.0% | 80.0% |
The calendar signal was directional rather than uniform: October and June had the clearest faster medians, while December was the clearest high-risk month. For planning, a December EU submission carried a 6.1-fold higher observed 90-day delay rate than October (80.0% versus 13.0%).
End to end CTIS timing rose to a 124.5-day median for submissions involving four or more countries, compared with 79 days for one country and 29.5 days for two to three countries. At country level, Part II timing rose from 87 days for one-site country packages to 232 days for two to five sites and 296.5 days for six or more sites.
The clearest operational risk was a large local site footprint: six-plus-site country packages had a Part II median 209.5 days longer than one-site packages, and 24 of 30 (80.0%) remained at 90 days or longer. Multi-country complexity became most visible at four or more countries, where 8 of 12 trials (66.7%) reached 90 days or longer end to end.
First-in-human trials had a 106-day median versus 62 days for other studies, with 18 of 30 (60.0%) taking at least 90 days. Exact Phase I studies had a 97-day median versus 55 days for Phase I/II studies. Orphan-designated studies moved faster in this cohort—42 days versus 81.5 days—but this is a descriptive cohort association, not a causal effect.
Novelty and early-phase intensity were more informative than most protocol-complexity counts. First-in-human status added 44 median days, and exact Phase I added 42 median days versus Phase I/II. In contrast, continuous measures such as sample size, eligibility criteria and endpoint counts showed no meaningful monotonic correlation with review time (absolute Spearman ρ values ≤0.14).
The matrix compares the same factors against three practical outcomes: below the 77-day end to end median, at least 60 days, and at least 90 days. October submissions and orphan designation were the strongest faster-than-median signals, while December submission, four or more countries and first-in-human status concentrated the largest 90-day delay shares.
| Factor | Below 77d | ≥60d | ≥90d |
|---|---|---|---|
| October submissions n=23; median 31 days |
78.3% | 26.1% | 13.0% |
| December submissions n=20; median 112 days |
15.0% | 85.0% | 80.0% |
| 2–3 countries n=12; median 29.5 days |
75.0% | 25.0% | 25.0% |
| 4+ countries n=12; median 124.5 days |
33.3% | 66.7% | 66.7% |
| Orphan-designated trials n=17; median 42 days |
76.5% | 23.5% | 17.6% |
| First-in-human trials n=30; median 106 days |
36.7% | 63.3% | 60.0% |
| 6+ sites n=36; median 98 days |
47.2% | 58.3% | 52.8% |
A practical high-risk profile combines a late-year submission, first-in-human development and a broad country or site footprint. The lower-risk signals in this dataset were October or June submission timing and a two-to-three-country footprint; however, all associations are descriptive and should support contingency planning rather than deterministic forecasting.
CTIS means the Clinical Trials Information System. End to end timing is the calendar interval from initial CTIS/EU submission to first CTIS authorization. Country Part II timing is the calendar interval from the earliest country-specific Part II submission to the latest recorded decision or authorization for that country. “Shorter than median” means below 77 days; substantial delay is reported at 60 days and 90 days or longer. Submission year was excluded as an explanatory factor.