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wxp ☆ China, 2013-10-17 17:21 (4240 d 08:07 ago) Posting: # 11677 Views: 6,470 |
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Dear all, I have a problem with the ISR of an unstable drug. We are doing a PK study of an unstable drug. We have found that adding vitamin C into the plasma samples can keep the drug stable under -80℃ for at least 1 month (the stability test is still going on). In this study, our subjects are patients, 18 blood samples per subject, and we can predict that the recruitment may take a long time. Here are the questions: 1. We should do the ISR within the stable period we tested (1 month for now),right? If there are only blood samples of one or two subjects, should we still do the ISR? It will cause several batches of ISR, but only 2~4 samples each batch?  2. Can we just add the ISR samples in the next batch of the unknown ones? Any comments in this regard will be highly appreciated. Hope the drug keeps stable longer! — Best regards, Xipei China |
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sarada06884 ☆ India, 2013-10-18 09:49 (4239 d 15:39 ago) @ wxp Posting: # 11684 Views: 5,534 |
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Dear Xipei, As you have said, ISR should be performed within the stability period of the drug. This means that the stability period of the drug starts right from the time of first sample collection. For this you have have proven data handy regarding the stability of the sample. As in your case this is only 01 month it would be better if you start early. Even though the stability test is still going on, remember "A bird at hand is worth two in the bush". Imagine the consequence if the stability fails!!! Now as per your question there is not other option but to perform ISR even though thsi means only 2~4 samples each batch. There is absolutely nothing wrong with this but it is suggested that the ISR of samples be performed on a different day but within the proven stability duration (See EMEA BMV Sec 6:It is therefore recommended to evaluate accuracy of incurred samples by reanalysis of study samples in separate runs at different days). IMHO adding the ISR samples in the next batch of the unknown ones would not be considered as a good option. Regards P.S.Srinivas |
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wxp ☆ China, 2013-10-18 11:02 (4239 d 14:26 ago) @ sarada06884 Posting: # 11690 Views: 5,519 |
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Thank you for your reply, Srinivas — Best regards, Xipei China |
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Ohlbe ★★★ France, 2013-10-18 16:39 (4239 d 08:49 ago) @ sarada06884 Posting: # 11699 Views: 5,514 |
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Dear Xipei and Srinivas, ❝ IMHO adding the ISR samples in the next batch of the unknown ones would not be considered as a good option. Why ? What is required is to re-analyse the samples in a separate run on a separate day. The usual practice is to analyse the ISR samples in dedicated runs, because there are quite a lot of samples to analyse. In this case it would make little sense to have a run with a calibration curve and 2 sets of QCs just for 3-4 samples. A pragmatic approach would indeed be to add them to the next routine run. It would indeed be safer to start analysing the samples while they are in their demonstrated stability period, if the analyte is known to be unstable. Once you have obtained extended stability data you may be able to wait for more time and analyse more samples in dedicated runs if preferred. Still, it is good to have at least some data early in the trial: if something goes wrong it is always better to discover it in an early phase than at the end of the study, especially in a patient study with a long recruitment time. — Regards Ohlbe |
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wxp ☆ China, 2013-10-21 06:15 (4236 d 19:13 ago) @ Ohlbe Posting: # 11711 Views: 5,433 |
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❝ ...A pragmatic approach would indeed be to add them to the next routine run. I agree with you, Ohlbe. Thank you for your comments. — Best regards, Xipei China |
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sarada06884 ☆ India, 2013-10-21 13:55 (4236 d 11:33 ago) @ Ohlbe Posting: # 11716 Views: 5,458 |
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Dear Ohlbe, As per EMA's BMV Sec 6: "It is therefore recommended to evaluate accuracy of incurred samples by reanalysis of study samples in separate runs at different days". So doesn't this mean that they have to be run in seperate batches and the ISR be performed on diffrent day? I have come across a regulatory inspector who insisted that repeats samples be run in separate batches. In a study we had only a single repeat and since there was only a single repeat in the entire study we analyzed this repeat along with last batch of subject samples. This was properly named indicating that this was a repeat. The inspector insisted that even though there was a single repeat in the entire study this cannot be clubbed with subject samples although properly named and has to be repeated in a separate batch. So can be extrapolated to ISR samples also? Regards P.S.Srinivas |
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Ohlbe ★★★ France, 2013-10-21 14:01 (4236 d 11:27 ago) @ sarada06884 Posting: # 11717 Views: 5,376 |
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Dear Srinivas, ❝ As per EMA's BMV Sec 6:"It is therefore recommended to evaluate accuracy of incurred samples by reanalysis of study samples in separate runs at different days". So doesn't this mean that they have to be run in separate batches and the ISR be performed on diffrent day? My understanding is that each sample needs to be reanalysed in a separate run and on a different day from the initial analysis, not from any other analysis. ❝ I have come across a regulatory inspector who insisted that repeats samples be run in seperate batches. From which authority ? ❝ The inspector insisted that even though there was a single repeat in the entire study this cannot be clubbed with subject samples although properly named and has to be repeated in a separate batch. Did he give any explanation or justification for this requirement ? — Regards Ohlbe |
Ing. Helmut Schütz