Bioequivalence and Bioavailability Forum • Intra subject variability

maulik963
☆

India,
2011-10-05 18:27
(5370 d 14:49 ago)

Posting: # 7428
Views: 5,742

Intra subject variability [Power / Sample Size]

Hi I am Maulik here.

I am a new member of this family.

i am very much impressed with the topic that had discussion hence i am trying to solve my doubts.

hope i will be satisfied.

I have a question that if "A" drug having the intra subject variability >30% hence BE range will be broader than 80-125% now if i do a study with "A" drug considering as a standard and comparing my test drug "B" and i found intra subject variability <30% (by any reason) for "A" drug. Then my BE range will be more than 80-125% or it will be stringent to 80-125%?

I hope you understand.

Edit: Category changed. [Helmut]

Helmut
★★★

Vienna, Austria,
2011-10-05 19:51
(5370 d 13:25 ago)

@ maulik963
Posting: # 7429
Views: 4,924

Scaling?

Post reply

Dear Maulik!

❝ I am a new member of this family.

Welcome to the club.

❝ I have a question that if "A" drug having the intra subject variability >30% hence BE range will be broader than 80-125% now if i do a study with "A" drug considering as a standard and comparing my test drug "B" and i found intra subject variability <30% (by any reason) for "A" drug. Then my BE range will be more than 80-125% or it will be stringent to 80-125%?

❝

❝ I hope you understand.

Only if I substitute ‘drug’ by ‘formulation’. If you have a highly variable drug (CV_intra of a solution >30%) I don’t expect to see a CV <30% for the formulation. The acceptance range for highly variable drugs / drug products (HVDs/HVDPs) depends on the regulation. Scaling or widening may be applicable, e.g.,

FDA: AUC and/or C_max if CV ≥30% in a replicate design
EMA: Only for C_max if no safety concerns (high variability alone is not enough) and CV >30% in a replicate design
Canada: Scaling for AUC under consideration, no confidence interval required for C_max (only T/R within 80–125%)
New Zealand: C_max 75–133% if no safety concerns, no replicate design necessary
Russia: C_max 75–133% (all drugs, no replicate design necessary)
…

If the CV_intra (of the reference!) in the study <30% you are not allowed to scale / widen the acceptance range. See FDA’s progesterone guidance (Step 1a) and EMA’s BE guideline (Section 4.1.10).

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

vinayshed ☆ 2011-10-06 16:46 (5369 d 16:30 ago) @ maulik963 Posting: # 7432 Views: 4,739	Intra subject variability Post reply
	Hi Maulik, If I have understood your question correctly, the 90% CI for your test formulation will be within 80 to 125%. If you are trying to know something else, pl clarify Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Helmut
★★★

Vienna, Austria,
2011-10-06 18:16
(5369 d 15:00 ago)

@ vinayshed
Posting: # 7435
Views: 4,728

Intra subject variability

Post reply

Dear Vinay,

great to have you here; congrat's to your first post. :ok:

❝ […] the 90% CI for your test formulation will be within 80 to 125%.

I would rather say: […] the 90% CI for your test formulation has to be within 80 to 125% (since CV <30% – no widening will be acceptable in many countries).

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes