Bioequivalence and Bioavailability Forum

Dear all!
The applicant wanted a wavier from Clinical end point study and so they have used a PBPK approach to prove that the levels of free drug in fluid are similar to reference product. As per the article- "The applicant conducted the PSG- recommended in vivo BE study with PK end points but did not perform the PSG- recommended comparative clinical end point study. Instead, the applicant developed a dermal PBPK model for a VBE assessment based on drug exposure at the presumed site of action between the reference and the test products."
The applicant choose- “the most accurate, sensitive, and reproducible approach available among those set forth" which is PK endpoint compared to clinical endpoint.
To further support- Q1, Q2 and Q3 (IVRT and IVPT) were compared against RLD.
Based on all the data- it is acceptable to presume that there is no significant difference between reference drug and applicant formulation. On the same basis- FDA has accepted the application.
Regards,
Dshah