Bioequivalence and Bioavailability Forum • Eealuaiton of repeat on new curve

auditor
★

India,
2011-07-04 10:57
(5084 d 17:29 ago)

Posting: # 7205
Views: 3,880

Eealuaiton of repeat on new curve [Bioanalytics]

Dear All,

In one of the study it is observed that the validaiton range is not enough to cover the subject sample analysis as most of the sample of the intial analysis were idnetified under repeat due to "Above ULOQ".

The curve was redifend and the remaining study samples were analyzed based on the new curve. Now the question is, whatever samples which are fall into the repeat due to "Above ULOQ" were repeated under new curve.

I personally belive that the repeatation of the sample time point which are goes beyond the ULOQ should be repeted under the same curve instead of repeting under the new revised curve.

Kindly correct me if my understnading is wrong.

regards

Auditor.

Edit: See this post, please! [Helmut]

Ohlbe
★★★

France,
2011-07-04 20:52
(5084 d 07:34 ago)

(edited on 2011-07-06 14:32)
@ auditor
Posting: # 7206
Views: 3,211

Evaluation of repeat on new curve

Post reply

Dear Auditor,

If I understand correctly your concern:

you validated a method with a given range (let's say 1 to 100 ng/ml)
after analysing a few subjects, you realised that the range was too low, as many samples were above ULOQ
you expanded the range (let's say 1, or possibly 2, to 200 ng/ml)
you now wonder whether above ULOQ samples should be re-analysed with the short range (1 to 100) after a dilution, or with the expanded range (1 to 200) without dilution, and you would prefer the first option.

I think it would be OK to have the samples re-analysed with the wider range and no dilution (supposing you have re-validated the method with the new range, of course). One could object that these samples will be analysed with different conditions compared with samples from the same subject which were below ULOQ, and that it may create some disruption in the PK profiles. On the other hand you will avoid the influence of a dilution (and of possible differences in matrix effects between your subject plasma and blank plasma).

What reason made you prefer to re-analyse the samples with the initial range ?

Regards
Ohlbe

—
Regards
Ohlbe

auditor
★

India,
2011-07-05 11:01
(5083 d 17:25 ago)

(edited on 2011-07-05 14:02)
@ Ohlbe
Posting: # 7208
Views: 3,208

Evaluation of repeat on new curve

Post reply

Dear Ohlbe,

My concern is, if we analyze the sample with the wider range then the situation is half of the subject samples are quantified by one curve (old one) and the repeat samples are analyzed on revised curve wich is containing my Cmax of that perticuler subject. Hence due to estimation of Cmax of the repeated subject time point is done on the other curve, i feel that, it should be repeated under old curve only after applying dilution and reprot the value.

Regards

Auditor

Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

swapnil.kuche
★

2011-07-05 11:46
(5083 d 16:40 ago)

@ auditor
Posting: # 7210
Views: 3,208

Evaluation of repeat on new curve

Post reply

Dear Auditor,

I am totally agree with the Ohlbe. :cool:

While switch over to new calibration range obviously you had perform partial validation. :confused:

If your method is partially validated properly there is no problem to analyse old identified repeats under new calibration curve.

Believe me we had done the same in USFDA submission study and it was accepted by regulators provided that your Repeat Analysis SOP should be very much clear on such issues. ;-)

Regards,
Swapnil D. Kuche