jag009
★★★

NJ,
2018-09-10 18:41
(808 d 07:13 ago)

Posting: # 19257
Views: 3,922
 

 f2 computation (for pts > 85%) [Dissolution / BCS / IVIVC]

Hi all,

One question related to f2 computation... According to guidance you only include one pt after 85 % release. But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right?

Thanks
John


Edit: Category changed; see also this post #1[Helmut]
ElMaestro
★★★

Belgium?,
2018-09-10 22:52
(808 d 03:03 ago)

@ jag009
Posting: # 19258
Views: 3,406
 

 f2 computation (for pts > 85%)

Hi jag,

» One question related to f2 computation... According to guidance you only include one pt after 85 % release. But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right?

Where does that concept come from? And could you put more words to it?
Also, I am thinking a plateau is something which is hard to debate in a purely measurable way.

Muy confundido :confused:

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.
jag009
★★★

NJ,
2018-09-12 00:00
(807 d 01:55 ago)

@ ElMaestro
Posting: # 19262
Views: 3,144
 

 f2 computation (for pts > 85%)

» » One question related to f2 computation... According to guidance you only include one pt after 85 % release. But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right?
»
» Where does that concept come from? And could you put more words to it?
» Also, I am thinking a plateau is something which is hard to debate in a purely measurable way.
»
» Muy confundido :confused:

NOT me! My boss said so... I was wondering too.
Does it matter if the drug is an ER or IR?

Thx
John
Obinoscopy
★    

USA,
2018-09-11 20:21
(807 d 05:34 ago)

@ jag009
Posting: # 19260
Views: 3,251
 

 f2 computation (for pts > 85%)

» One question related to f2 computation... According to guidance you only include one pt after 85 % release.

Yes.

» But for drugs that don't show plateau after 85% (ie; even at one pt after 85%, the curve is still climbing) you have to include addition points right?

I don't think so. Once 85% dissolution has been achieved, then we can calculate for f2.

Was told 85% is a sacred clinical number (don't ask who told me ;-)). Was told once 85% of a drug dissolves within the expected time the drug gets to the intestine, then it is very bioavailable. Whatever happens beyond the 85% is just additional info which isn't critical.

Based on this, I think 85% is the determinant. Only if 85% is not achieved then we now check when plateau is reached.

Not sure though. Perhaps I'm mixing up biowaivers dissolution with other form of dissolution studies.

Scopy
jag009
★★★

NJ,
2018-09-12 00:01
(807 d 01:53 ago)

@ Obinoscopy
Posting: # 19263
Views: 3,171
 

 f2 computation (for pts > 85%)

Hi,

» Based on this, I think 85% is the determinant. Only if 85% is not achieved then we now check when plateau is reached.
»
» Not sure though. Perhaps I'm mixing up biowaivers dissolution with other form of dissolution studies.

Thanks but the person who told me insisted that it is the correct way :confused::confused::confused:

john
Obinoscopy
★    

USA,
2018-09-12 00:38
(807 d 01:17 ago)

@ jag009
Posting: # 19264
Views: 3,154
 

 f2 computation (for pts > 85%) - WHO GL

» Thanks but the person who told me insisted that it is the correct way :confused::confused::confused:

I just checked the WHO interchangeability guideline, it states:

"a maximum of one-time point should be considered after 85% dissolution of the reference (comparator) product has been reached; in the case where 85% dissolution cannot be reached...the dissolution should be conducted until an asymptote (plateau) has been reached"

I don't know what the USFDA GLs say though.

I guess person who told you has a lot of explaining to do. I for one, am very interested in his explanation.

Regards,

Scopy
Helmut
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Homepage
Vienna, Austria,
2018-09-12 01:01
(807 d 00:53 ago)

@ Obinoscopy
Posting: # 19265
Views: 3,096
 

 f2 computation (for pts > 85%) - WHO GL

Hi Scopy & John,

» I don't know what the USFDA GLs say though.

Remember that one and followings?

Dif-tor heh smusma 🖖
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. 🚮
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jag009
★★★

NJ,
2018-09-12 20:35
(806 d 05:19 ago)

@ Obinoscopy
Posting: # 19280
Views: 3,092
 

 f2 computation (for pts > 85%) - WHO GL

Hi,
» I don't know what the USFDA GLs say though.
» I guess person who told you has a lot of explaining to do. I for one, am very interested in his explanation.

But if you do end up computing f2 using all pts? What's the harm in that? Isn't it better to conclude based on a complete profile? (meaning stop when plateau is evident. Of course this term plateau is kinda of objective.

Example:
Time: 1,2,3,4,6,8,10,12
R: 27,42,54,62,76,86,92,96
T: 34,51,64,73,87,94,98,99

If we go by the definition out there then you would cut off at 8 hours. But if you compute f2s at 8 hrs cutoff vs 12 hrs then the 8 hr cutoff f2 will fail (<50). At 8 hrs the profile isn't really complete (visually).

Thank
John
ElMaestro
★★★

Belgium?,
2018-09-12 22:02
(806 d 03:53 ago)

@ jag009
Posting: # 19281
Views: 3,117
 

 f2 computation (for pts > 85%) - WHO GL

Hi jon,

» But if you do end up computing f2 using all pts? What's the harm in that? Isn't it better to conclude based on a complete profile? (meaning stop when plateau is evident. Of course this term plateau is kinda of objective.

No, actually there could be a good reason not to do that.
Consider very early and very late time points. Even if the two curves are shifted, the very early points could be close to zero dissolution, and the very late time points could close to maximum dissolution. for both. Inclusion of (many of) those points in a quantitative comparison will skew the conclusion towards similarity. You absolutely want to assure that you are capturing mainly the "steep" part of the curves. The sexy stuff in dissolution happens right where you are neither very early nor very late.

A comparison of plateau levels say nothing about product performance but just about relative maximum dissolution.

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.
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