Table 4. Results of bioequivalence testing using average bioequivalence (ABE) and scaled average bioequivalence (SCABE) metrics for the area under the curve (AUC) (A), maximum concentration (Cmax) (B), and the minimum concentration (Cmin) (C) in individuals with a kidney transplant.
| (A) AUC | |||||||||
| Reference | Test | AUC geometric mean ratio (%) | Reference within-subject variability (SWR, %) | Observed 90% confidence interval | Confidence bound | SCABE limit | Variability comparison (1statistics of σWT/σWR) | Product approval standards | |
| FDA2 | EMA3 | ||||||||
| Innovator | Generic Hi |
105.47 | 12.11 | 101.44–109.65 | −0.0060 | 88.02–113.61 | 1.62 | Pass | Pass |
| Innovator | Generic Lo |
105.95 | 12.11 | 100.85–111.30 | −0.0035 | 88.02–113.61 | 1.75 | Pass | Fail |
| Generic Hi |
Generic Lo |
100.46 | 14.62 | 95.45–105.72 | −0.0163 | 85.72–116.65 | 1.45 | Pass | Pass |
| Generic Lo |
Generic Hi |
99.54 | 15.81 | 94.59–104.76 | −0.0192 | 84.65–118.13 | 1.24 | Pass | Pass |
| (B) CMAX | |||||||||
| Reference | Test | CMAX geometric mean ratio (%) | Reference within-subject variability (SWR, %) | Observed 90% confidence interval | Confidence bound | SCABE limit | Variability comparison (1statistics of σWT/σWR) | Product approval standards | |
| FDA2 | EMA3 | ||||||||
| Innovator | Generic Hi |
108.68 | 22.74 | 102.77–114.94 | −0.0293 | 80.00–125.00 | 1.46 | Pass | Pass |
| Innovator | Generic Lo |
109.80 | 22.74 | 101.06–119.29 | −0.0207 | 80.00–125.00 | 1.12 | Pass | Pass |
| Generic Hi |
Generic Lo |
101.02 | 24.72 | 93.69–108.93 | −0.0469 | 80.00–125.00 | 1.03 | Pass | Pass |
| Generic Lo |
Generic Hi |
98.99 | 18.99 | 91.81–106.73 | −0.0266 | 81.86–122.16 | 1.75 | Pass | Pass |
| (C) CMIN | |||||||||
| Reference | Test | CMIN geometric mean ratio (%) | Reference within-subject variability (SWR, %) | Observed 90%confidence interval | Confidence bound | SCABE limit | Variability comparison (1statistics of σWT/σWR) | ||
| Innovator | Generic Hi |
104.85 | 12.24 | 100.74–109.12 | −0.0071 | 87.90–113.77 | 1.24 | ||
| Innovator | Generic Lo |
104.48 | 12.24 | 99.68–109.51 | −0.0067 | 87.90–113.77 | 1.66 | ||
| Generic Hi |
Generic Lo |
99.65 | 11.33 | 94.81–104.73 | −0.0094 | 88.75–112.68 | 1.80 | ||
| Generic Lo |
Generic Hi |
100.36 | 15.14 | 95.49–105.48 | −0.0177 | 85.25–117.30 | 1.01 | ||
EMA, European Medicines Agency; FDA, US Food and Drug Administration; σWR, within-subject standard deviation for the reference product; σWT, within-subject standard deviation for the test product.
1Upper limit of the 90% confidence interval of the ratio of within-subject standard deviation of test product to reference product, σWT/σWR.
2FDA product approval standards for SCABE require the AUC and the CMAX observed 90% confidence intervals to fall within the SCABE limit.
3EMA product approval standards for tacrolimus ABE require the observed 90% confidence interval to fall within 90.00%–111.10% for AUC and within 80.0%–125.0% for CMAX.