Model-based bioequivalence methods open new doors for generics
Presented by
henrik.bjugard.nyberg@pharmetheus.com
Background
Traditional bioequivalence (BE) via Non-Compartmental Analysis (NCA) requires prohibitive sample sizes for complex drugs (LAIs/HVDs), creating barriers to affordable generics. Model-Based Bioequivalence (MBBE) maintains regulatory rigor (Type I error control) while improving efficiency.
The objective was to demonstrate MBBE’s practical value in increasing study power and reducing costs.
Methods
Methods
This example used a 2-way crossover study of a moderately variable oral drug (~50% IIV, ~15% IOV). Sample size required for 80% statistical power.
MBBE
Single-model method with sampling-importance-resampling (SIR) uncertainty.
NCA
Power calculations via powerTOST R package
Results
Results
MBBE significantly reduced the required sample size compared to NCA while maintaining target power.
- N for 80% Power – MBBE: 24, NCA: 44
- Power at N=24 — MBBE: 80%, NCA: 58%
Publications
Recommended reading
-publication 1
publication 2
publication 3