Vishal S
☆    

India,
2021-08-06 11:12
(41 d 09:01 ago)

(edited by mittyri on 2021-08-09 11:37)
Posting: # 22514
Views: 1,488
 

 Biowaiver for lower strength [Study Per­for­mance]

Hii Helmut

In USFDA submissions we have successfully conducted BE study on 20 mg strength(higher) as per FDA draft guidance under fasting & Fed conditions and Appling for Waiver request of in vivo testing: 2.5 mg, 10 mg and 15 mg strengths based on
(i) acceptable BE studies on the 20 mg strength,
(ii) proportional similarity across all strengths, and
(iii)acceptable in vitro dissolution testing of all strengths
However for 2.5 mg strength we are failed to submit in vitro dissolution data.
so-
Is we need to Conduct in vivo BE study for 2.5 mg Strength?

what is study condition for study either Fasting or Fed or Both fasting & Fed for 2.5 mg strength?

Some Notes are-
Our formulation is Immediate release Tablet formulation.

Drug demonstrates a steep exposure-response relationship for both efficacy and safety.

pharmacokinetics are approximately linear up to about 15 mg once daily in fasting state.
Under fed conditions Drug 10 mg, 15 mg and 20 mg tablets demonstrated dose-proportionality.

At higher doses Drug displays dissolution limited absorption with decreased bioavailability and decreased absorption rate with increased dose.


Thanks
Vishal S


Edit: Category changed; see also this post #1. Please follow the Forum’s Policy[Mittyri]
drgunasakaran1
★★  
avatar

2021-08-06 14:47
(41 d 05:26 ago)

@ Vishal S
Posting: # 22515
Views: 1,138
 

 Biowaiver for lower strength

Dear Mr Vishal,

» However for 2.5 mg strength we are failed to submit in vitro dissolution data.

Kindly clarify whether you failed to submit the in vitro dissolution data of 2.5mg or after in vitro testing, the 2.5mg strength does not show proportional similarity and acceptable in vitro dissolution testing.

» Is we need to Conduct in vivo BE study for 2.5 mg Strength?
» what is study condition for study either Fasting or Fed or Both fasting & Fed for 2.5 mg strength?

I hope the molecule of interest is Rivaroxaban. Kindly confirm the molecule (if possible) to provide the appropriate response for your query on requirement of fasting/fed study for 2.5 mg strength.

Dr S Gunasakaran MBBS MD
Disclaimer: The replies/posts are my personal opinions and it does not represent my company views on the same.
Vishal S
☆    

India,
2021-08-09 08:55
(38 d 11:17 ago)

(edited by mittyri on 2021-08-09 11:34)
@ drgunasakaran1
Posting: # 22518
Views: 474
 

 Biowaiver for lower strength

Dear sir

» Kindly clarify whether you failed to submit the in vitro dissolution data of 2.5mg or after in vitro testing, the 2.5mg strength does not show proportional similarity and acceptable in vitro dissolution testing.

clarification-after in vitro testing, the 2.5mg strength does not show proportional similarity and acceptable in vitro dissolution testing.

Thanks
Vishal S



Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Mittyri]
luvblooms
★★  

India,
2021-08-18 10:34
(29 d 09:39 ago)

@ Vishal S
Posting: # 22527
Views: 351
 

 Biowaiver for lower strength

Hi Vishal

» clarification-after in vitro testing, the 2.5mg strength does not show proportional similarity and acceptable in vitro dissolution testing.

A common problem with drugs that have dose-dependent solubility.
The best way to handle this scenario is to go with does equivalent dissolution approach (assuming your formulation is dose-proportional).

Example:

2.5 mg *8 vs 20 mg
5 mg*4 vs 20
10mg *2 vs 20

There are few SBoA's available where FDA has recommended this approach.
I am trying to find those and will update the post if I am able to get those.

~A happy Soul~
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