Bioequivalence and Bioavailability Forum • Widening Cmax in EU

Clarc
☆

Romania,
2013-10-24 16:55
(4220 d 03:19 ago)

Posting: # 11748
Views: 5,684

Widening Cmax in EU [RSABE / ABEL]

Dear All

We have to perform a bioequivalence on a HVD in EU.
The intrasubject variability in the literature is 29%, 32% and 36%.
Our statistical software doesn't permit scaling, only widening to 0.75-1.33.
The design is a fully replicated TRTR/RTRT design.

So my question is:
Can I define in the protocol a widening to 0.75-1.33, or I have to perform a reference scaled bioequivalence?

Thanks

—
I'm always tryin' to do something new, tryin' to look like a beginner.
Meshell Ndegeocello

drgunasakaran1
★★

2013-10-24 17:43
(4220 d 02:31 ago)

@ Clarc
Posting: # 11751
Views: 4,852

Widening Cmax in EU

Post reply

Dear Clarc,

❝ Can I define in the protocol a widening to 0.75-1.33, or I have to perform a reference scaled bioequivalence?

For EU submission, it is suggested to go for Expandable BE limits as per EMA's Guideline on the Investigation of Bioequivalence

—
Dr Gunasakaran Sambandan MD
Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn

Helmut
★★★

Vienna, Austria,
2013-10-25 16:56
(4219 d 03:18 ago)

@ Clarc
Posting: # 11768
Views: 4,761

EMA: ABEL

Post reply

Hi Clarc,

❝ Our statistical software doesn't permit scaling, only widening to 0.75-1.33. The design is a fully replicated TRTR/RTRT design.

May I guess: Kinetica? If yes, AFAIK you cannot evaluate replicate designs at all.

❝ Can I define in the protocol a widening to 0.75-1.33,

You could, but it will not be accepted…

❝ or I have to perform a reference scaled bioequivalence?

Yes – see Dr. Gunasakaran’s post above. Don’t forget two obstacles:

A sound justification that a wider difference in C_max is clinically irrelevant.
A justification that the calculated intra-subject variability is a reliable estimate and that it is not the result of outliers.

—
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

Clarc
☆

Romania,
2013-10-28 11:04
(4216 d 08:10 ago)

@ Helmut
Posting: # 11790
Views: 4,585

EMA: ABEL

Post reply

Dear Dr.S.Gunasakaran, Dear Helmut

Thanks for the replies, and for the advices.

❝ May I guess: Kinetica?

Yes, You may... and Yes unfortunately... it is Kinetica.

❝ Don’t forget two obstacles:

A sound justification that a wider difference in C_max is clinically irrelevant.
❝
A justification that the calculated intra-subject variability is a reliable estimate and that it is not the result of outliers.

Of course I will not forget about these...

Thanks again.

—
I'm always tryin' to do something new, tryin' to look like a beginner.
Meshell Ndegeocello