Bioequivalence and Bioavailability Forum • HVDP RSABE (FDA) and ABEL (EMA)

khaoula
★

Algeria,
2014-05-20 21:18
(4011 d 14:46 ago)

Posting: # 12978
Views: 6,907

HVDP RSABE (FDA) and ABEL (EMA) [RSABE / ABEL]

Hi everybody,

I'm pharmacist doing my residency in pharmacology in Algeria, I prepare my post graduate disertation and the subject is the design of bioequivalence studies for Highly Variable Drug,

I try to understand the two approche of EMA and FDA for HVDP:

EMA:- does The European guideline prescribes a pilote study with replicate design to determine a CV withinsubject of the reference product to expand the limits in a pivotal replicate design study and apply the TOST with the news limits?
- the sample size is determined with CV withinsubject of bibliography?

FDA: what about the TOST ? or we juste apply mixed procedure for average BE? I dont understand what they do
thank you very much and sorry I have a bad english :-)

d_labes
★★★

Berlin, Germany,
2014-05-22 16:24
(4009 d 19:41 ago)

@ khaoula
Posting: # 12989
Views: 5,780

HVDP RSABE (FDA) and ABEL (EMA)

Post reply

Dear khaoula,

❝ ... I prepare my post graduate disertation and the subject is the design of bioequivalence studies for Highly Variable Drug,

one of the main activity of a scientist, and you will become such a strange person, is reading papers of their colleges :cool:

.
There are tons of papers out there dealing with your subject. I recommend: Read them! To get an understanding what in principle could be done scientifically.
Read also the guidelines to notice what regulatory bodies left over from the scientific possibilities.

Wish you good luck
Detlew

khaoula
★

Algeria,
2014-05-23 17:37
(4008 d 18:27 ago)

@ d_labes
Posting: # 12997
Views: 5,789

HVDP RSABE (FDA) and ABEL (EMA)

Post reply

Dr Mr,
I have read à lot of guidelines and Draft of(FDA, EMA)and some articles but I do not have access to lot of papers such as http://www.ncbi.nlm.nih.gov/pubmed/22162308 , so I can't understand for FDA approach application of SABE The test formulation is judged to be SABE with the reference product if the upper 95% confidence limit is <0 and after applie the TOST for the new limits or no, thank you :-)

Helmut
★★★

Vienna, Austria,
2014-05-23 19:11
(4008 d 16:53 ago)

@ khaoula
Posting: # 12998
Views: 5,818

Some hints

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Dear Khaoula,

❝ […] The test formulation is judged to be SABE with the reference product if the upper 95% confidence limit is <0 and after applie the TOST for the new limits or no

The general model (both for RSABE and ABEL) is

(I) –θ_s ≤ (μ_T–μ_R)/σ_W ≤ θ_s.

We can rearrange this inequation to

(II) –θ_sσ_W ≤ μ_T–μ_R ≤ θ_sσ_W.

That’s the model used by the EMA. The conventional 90% confidence interval should lie within the scaled (i.e., widended) acceptance limits. Therefore, the name of the method is Average Bioequivalence with Expanding Limits (ABEL).

The FDA went another path. Start from (II) and square all sides in order to obtain:

(III) θ_s²σ_W² ≤ (μ_T–μ_R)² ≤ θ_s²σ_W².

Homework:

The algebra to get (μ_T–μ_R)² – θ_s²σ_W² ≤ 0 from (III).
Find out why the FDA requires the upper 95% confidence limit to be ≤0.

For some references see this post. The paper by the two Lászlós is free.

—
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

ElMaestro ★★★ Denmark, 2014-05-23 20:34 (4008 d 15:31 ago) @ Helmut Posting: # 12999 Views: 5,749	Some hints Post reply
	Hi Hötzi, ❝ The FDA went another path. Start from (II) and square all sides in order to obtain: (III) θ_s²σ_W² ≤ (μ_T–μ_R)² ≤ θ_s²σ_W². Excuse me? — Pass or fail! ElMaestro

Helmut
★★★

Vienna, Austria,
2014-05-24 01:44
(4008 d 10:21 ago)

@ ElMaestro
Posting: # 13003
Views: 5,734

Maths dummy

Post reply

Mon capitaine!

❝ ❝ θ_s²σ_W² ≤ (μ_T–μ_R)² ≤ θ_s²σ_W².

❝ Excuse me?

Magnifique! Only proves that I’m lacking the most basic understanding of algebra. Go and get my pills now. :smoke:

—
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

khaoula ★ Algeria, 2014-05-23 22:56 (4008 d 13:08 ago) @ Helmut Posting: # 13000 Views: 5,758	Some hints Post reply
	thank you Helmut, I understood how we have (μT – μR)² – θs²·σW² ≤ 0. ^first ^next and: but why the upper limit and CI at 95 % that's the question !! , I will search !! thank you verry much !!