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RSABE - 95%UCB estimation for Highly variable Drugs_FDA

Scaled Bioequilence Highly Variable Drugs Upper Confidence Bound 95% BE FDA Estimation from SWR_&_SWT critbound

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Poll: SWR_AUC_FDA (0 member(s) have cast votes)

If Swr ______ then RSABE is permitted and acceptance criteria for 90% CI can be widened.

  1. <= 0.294 (0 votes [0.00%])

    Percentage of vote: 0.00%

  2. >= 0.294 (0 votes [0.00%])

    Percentage of vote: 0.00%

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#1 d_nil

d_nil

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Posted 18 November 2021 - 12:56 PM

Dear Team,

 

Is there any provision to determine Reference scaled average bioequivalence for Highly variable drugs?

In which, We are interested to calculate 95% Upper confidence bound. The parameter in which we are interested to estimate is critbound. How we can use WinNonlin (version 8.3.1.5014) to estimate it? Suggest if any additional module require for this.

 

We went through the AAPS Poster presentation,2013 

https://www.certara...._in_PHX_WNL.pdf

 

Note: I have an active license access towards Basic WinNonlin. (v 8.3.1.5014)

 

Kindly support by providing any relevant examples, Templates, Workflow etc.

 

Awaiting for your revert.

 

Regards,

d_nil


Regards,

d_nil


#2 Ana Henry

Ana Henry

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Posted 18 November 2021 - 03:50 PM

Dear D_nil,

You can find the updated templates for RSABE for HVD at the link below:

 

 

https://www.certarau...m/store/2383230

 

 

These templates calculate the critical bound parameter you mention.  Please make sure to download the templates for version 8.3.3. of Phoenix and read the instructions.

 

Sincerely,

Ana Henry


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#3 d_nil

d_nil

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Posted 19 November 2021 - 10:27 AM

Hi Ana,

 

Thank you for giving valuable time.

 

Its meeting my criteria.

 

Thanks..! :)

 

Regards,

d_nil


  • Simon Davis likes this

Regards,

d_nil


#4 Helmut Schütz

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Posted 20 November 2021 - 10:32 PM

Hi d_nil,

 

did you initiate the poll? If yes, the second part of the question is wrong.

 

Widening the acceptance range for the 90% is applicable for Average Bioequivalence with Expanding Limits (ABEL) if CVwR > 30%. That’s the approach used in all jurisdictions except the U.S. FDA and China’s CDE.

 

For these two agencies you have to apply Reference-scaled Average Bioequivalence (RSABE). That’s a different pot of tea. If swR < 0.294 (CVwR < 0.3004689) you have to apply conventional ABE. If swR ≥ 0.294 you may apply RSABE.

 

See the FDA’s Draft Guidance – Appendix B and a comparison.

 

As shown in the article, you may face problems if you have to evaluate a partial replicate study for ABE (happens quite often if you may scale Cmax but not AUC due to its lower variability). Avoid the lousy partial replicate design whenever possible.

 

 

 

 


 Best regards,
Helmut

http://forum.bebac.at/


#5 d_nil

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Posted 22 November 2021 - 05:22 AM

Hi Helmut,

 

The poll was not initiated,

 

I understand the differences among criteria for Both agencies with respect to ABE & RSABE.

 

Also, i appreciate your add-on comment on study design.

 

Regards,

d_nil


Regards,

d_nil






Also tagged with one or more of these keywords: Scaled Bioequilence, Highly Variable Drugs, Upper Confidence Bound, 95%, BE, FDA, Estimation from SWR_&_SWT, critbound

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