Bioequivalence and Bioavailability Forum

Hi Anu,

❝ […] as per Current effective EU guidance “Questions & Answers: Positions on specific questions addressed to the pharmacokinetics working party, Revision 7” does not categorically specify this molecule into NTI category.

EMA does not (and does not intent to) publish a list of NTIDs. The Q&A summarizes the outcome of referral procedures (i.e., applicants and member states’ regulators disagreed and requested a decision by EMA’s CHMP). If a drug is not listed in the Q&A it only means that no study went through a referral so far. In other words, if all applicants and European regulators agree that a drug has a NTI, you will never find the drug mentioned in the Q&A.*

❝ Kindly suggest whether we can design a study with a normal acceptable range (80-125)% for Cmax and AUCt or with the acceptance range of (90-111)% considering NTI.

Personally I would follow the PK working party’s recommendations for tacrolimus (90.00–111.11% for AUC and 80.00–125.00% for C_max). If in doubt seek scientific advice, as already suggested.

---

• Therefore, I don’t expect to see digoxin and warfarin ever to be mentioned in the Q&A.