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tarak_desai ☆ India, 2014-12-16 07:51 (3798 d 23:41 ago) Posting: # 14076 Views: 10,378 |
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Hello to all, Need your guidance on following case. In a two period, single dose, cross over, BE study, it was observd that after completion of period-I, there was insufficient quantity of the reference product available to dose subjects in period-II. sponsor also doesnt have same batch reference product availalbe with them. can we use the different batch reference product in priod-II? and what other measures to be taken in this case? or redosing to be done using same batch in period-I and II or do we need to cancel study? pls guide. thanks. tarak Edit: Category changed. [Helmut] |
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cher0424 ☆ China, 2014-12-16 08:31 (3798 d 23:02 ago) @ tarak_desai Posting: # 14078 Views: 8,929 |
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Hello Tarak: Reference product in BE study need can be different batch. It is provide more sufficient evidences for bioequivalence. |
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ElMaestro ★★★ Denmark, 2014-12-16 10:01 (3798 d 21:31 ago) @ tarak_desai Posting: # 14079 Views: 8,984 |
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Dear tarak_desai, ❝ In a two period, single dose, cross over, BE study,it was observd that after completion of period-I, there was insufficient quantity of the reference product available to dose subjects in period-II. sponsor also doesnt have same batch reference product availalbe with them. ❝ ❝ can we use the different batch reference product in priod-II? ❝ and what other measures to be taken in this case? Forgive me for saying this, I know this could be seen as a negative comment; But do you really think it is a good idea to proceed with this trial if you realise halfway through it that you have not been able to plan it well enough to have the Ref available in quantities sufficing for the number of subjects? It sounds to me like the planning is completely off. Think about responsibilities, futile trials, drug accountability, and GCP. (let me add: an argument of having to involve a new Ref batch to avoid the trial becoming futile strikes me as backward) — Pass or fail! ElMaestro |
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cher0424 ☆ China, 2014-12-16 10:31 (3798 d 21:01 ago) (edited on 2014-12-16 11:04) @ ElMaestro Posting: # 14080 Views: 8,915 |
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Hello ElMaestro: It indeed haven't prepare well for the trial, but the different between two batch should be within 5%, so particularly no much influence in trial result. Unless the test product quality happen on the edge of 80%-125%. In that case the differences between two batch are essential to pass or fail. 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! [Ohlbe] |
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Helmut ★★★   Vienna, Austria, 2014-12-16 14:36 (3798 d 16:56 ago) @ cher0424 Posting: # 14083 Views: 8,959 |
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Hi cher0424 & Tarak, I agree with what ElMaestro wrote about study planning etc. ❝ […] but the different between two batch should be within 5%, so particularly no much influence in trial result. Unless the test product quality happen on the edge of 80%-125%. In that case the differences between two batch are essential to pass or fail. Let’s play the devil’s advocate. CVintra 25%, CVtotal 50%, expected T/R 95%, 2×2 crossover study planned for ≥80% power. We would design the study with 28 subjects (expected power 80.7%). Let’s further assume that both the measured content of the first batch of the reference (R1) and of the test (T) were 100%. The true – though unknown – bioavailability of T is 95%. You try hard to find a second batch of the reference which matches R1 but the only one you could get had a measured content of 95% (within ±5% of both R1 and T). If you evaluate only the first period as a parallel design (bad idea, since Freeman* showed that you don’t get unbiased estimates if the study was planned a s a crossover):
Same story if you look only at the second period:
The CV employed in study planning was an assumption. What if it would be larger, say 40%? T/R1 (as planned) would fail with a lower CL of 79.70% but pass with T/R (lower CL 81.77%). Very bad idea. No regulator would buy that – for good reasons. 
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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cher0424 ☆ China, 2014-12-17 02:49 (3798 d 04:44 ago) @ Helmut Posting: # 14088 Views: 8,905 |
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Dear Hulmet Thank you for your vivid assumption. I still have one query. So if change the batch of Reference, the regulator need sponsor to provide separate and total analysis for each period ? |
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Ohlbe ★★★ France, 2014-12-17 14:45 (3797 d 16:48 ago) @ cher0424 Posting: # 14092 Views: 8,770 |
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Dear cher0424, ❝ So if change the batch of Reference, the regulator need sponsor to provide separate and total analysis for each period ? I think it is much, much simpler than that. If you change the batch of the reference product in the middle of the study, regulators are very likely to reject the study whatever analyses you provide. — Regards Ohlbe |
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Helmut ★★★ Vienna, Austria, 2014-12-17 15:49 (3797 d 15:43 ago) @ cher0424 Posting: # 14095 Views: 8,744 |
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Hi cher0424, ❝ Dear Hulmet Helmut, if you don’t mind. ❝ So if change the batch of Reference, the regulator need sponsor to provide separate and total analysis for each period ? My example demonstrates how different batches will influence the outcome. That’s exactly why I wrote: ❝ ❝ No regulator would buy that – for good reasons. No way. Forget it! — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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cher0424 ☆ China, 2014-12-18 02:08 (3797 d 05:24 ago) @ Helmut Posting: # 14099 Views: 8,739 |
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Hi Helmut|
jag009 ★★★ NJ, 2014-12-16 16:24 (3798 d 15:08 ago) @ tarak_desai Posting: # 14086 Views: 8,871 |
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Hi, ❝ In a two period, single dose, cross over, BE study, it was observd that after completion of period-I, there was insufficient quantity of the reference product available to dose subjects in period-II. sponsor also doesnt have same batch reference product availalbe with them. FDA? Good luck. Best thing to do is file a control correspondence and keep your fingers crossed. John |
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felipeberlinski ☆ Brazil, 2014-12-17 21:16 (3797 d 10:16 ago) @ jag009 Posting: # 14098 Views: 8,755 |
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ANVISA? No way too  |
Ing. Helmut Schütz