As R&D leaders, we often approve programs that look flawless on paper.
Same API. Same grade.
Formulation physicochemical characteristics aligned.
Dissolution behaved as expected.
Yet the BE study returned an uncomfortable result: Cmax dipped. AUC slipped. Bioequivalence failed.
The investigation followed the usual path: formulation, process, controls. None were the root cause.
The real issue was an assumption made early and rarely challenged:
“The API is the same.” Chemically, it was. Functionally, it was not.
Subtle differences in particle size distribution, crystal habit, polymorphism, surface energy, and manufacturer specific processing history translated into measurable PK impact.
That experience reinforced a principle I now emphasize across teams:
In oral solids, API sameness is not a specification, it is a performance behavior.
Most BE failures are not caused by late stage changes.They originate from early stage assumptions.
Read also: Understanding Bioequivalence: From Theory to Regulatory Approval
Resource Person: Bijayananda Sahoo