BE assessment regarding first time point Cmax [Study As­sess­ment]

posted by Erkin – Turkey, 2018-12-28 21:57 (2001 d 21:00 ago) – Posting: # 19719
Views: 8,552

Dear ElMaestro and Mann,

I've got an e-mail from Dr. Leon Shargel & Dr. Patrick Noonan who are the authors of "Generic Drug Product Development - Solid Oral Dosage Forms" about the reference of the sentence:

"If these early samples were not collected, then those subjects with first point Cmax values should be dropped from the primary statistical analysis."

E-mail from Dr. Lean Shargel:
"I am sorry that you can not find the appropriate reference. You can email the FDA office of Generic Drugs, Division of Bioequivalence, However, due to Holidays, you may not get a response for some time. In general, the FDA does not like to drop subjects in a BE study. I have had this problem in the past and unfortunately had to re-do the study with a larger subject population. Very costly."

E-mail from Dr. Patrick Noonan:
Dear Erkin and Leon,

I would agree with Leon in that it would be unlikely that a regulatory agency would permit dropping subjects from a BE study. Upon review of the chapter, written quite a long time ago, I don’t agree with my own text. More likely, if a substantial # of subjects exhibit a first point Cmax and the study design didn’t include a sample between 5 and 15 min, the study design may be regarded as inadequate and the study results suspect. My interpretation is that all subjects would be included in the statistical analysis. The older guidance (from 2003) provides a clearer explanation than that provided in the 2013 guidance.

Best regards,


Patrick K. Noonan, PhD
PK Noonan Pharmaceutical Consulting, LLC

I hope that after ElMaestro's hallucinations ;-) and Dr. Leon Shargel's reviews, dropping subjects due to first point Cmax subject is closed.

Best Regards & Happy New Year,


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