Bioequivalence and Bioavailability Forum

Hi sudy,

❝ […] can we use RSABE approach in case if we get ISCV-reference > 30% for any one of the PK parameter Cmax or partial AUCs, instead of using 90% CI calculation to prove the bioequivalence?

The guidance clearly states:

The 90% confidence intervals of the geometric mean test/reference (T/R) ratios for the above five C_max and AUC metrics (C_max, AUC_0-T1, AUC_T1-T2, AUC_T2-T3, AUC_0-∞) should fall within the limits of 80-125%.

Without a controlled correspondence you will risk an RTR because according to

• B. Alternate BE Studies:
  • FDA will RTR an ANDA if the ANDA contains one or more in vivo studies that were not recommended in the BE guidance, without adequate justification. Adequate justification should include justification for an approach that deviates from FDA posted guidance, including data (Module 2.7 and Module 5) and appropriate references.

❝ The OGD recommendation did not discuss anything about this case, as we know that methylphenidate is not a HVD.

In my experience you will get the highest CV in the first partial AUC of the fasting study. I never saw a high CV of C_max… A CV_wR >30% of AUC_0-3 is extremely unlikely.

@John: Other experiences?