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auditor ★ India, 2012-02-10 07:50 (4838 d 12:19 ago) Posting: # 8091 Views: 9,397 |
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Dear All, In one of the our study we have observed some first point C-max value, 3 out of 54 observation of test product and 13 out of 108 observation of reference formulation. Kindly give your suggestion about how the agency will take this issue and is it affect the study? Regards, Auditor Edit: Category changed. [Helmut] |
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drgunasakaran1 ★★  2012-02-10 08:00 (4838 d 12:09 ago) @ auditor Posting: # 8092 Views: 8,438 |
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Dear Mr.Auditor, First point Cmax always raises the question about the actual measurement of true Cmax or not, due to inadequate early sampling time points. First point Cmax will be acceptable by US FDA, if you had one early time point between 05 and 15 minutes and additional 02 to 05 sampling time points within 01 hour of dosing. — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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rana ☆ India, 2012-08-18 08:48 (4648 d 12:21 ago) @ drgunasakaran1 Posting: # 9078 Views: 7,973 |
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❝ First point Cmax always raises the question about the actual measurement of true Cmax or not, due to inadequate early sampling time points. First point Cmax will be acceptable by US FDA, if you had one early time point between 05 and 15 minutes and additional 02 to 05 sampling time points within 01 hour of dosing. Dear Dr gunasakaran, one of our study we got first point cmax for some subjects our sampling points were 0.00, 0.50, 1.00 hr... and as per literature tmax is 1 hr to 4 hr. Whether US regulatory is accepting this fact? and does it show any impact in Pharmacokinetic & statistical analysis? Regards, rana. |
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drgunasakaran1 ★★ 2012-08-21 09:01 (4645 d 12:08 ago) @ rana Posting: # 9087 Views: 8,023 |
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Dear Mr Rana, ❝ Whether US regulatory is accepting this fact? and does it show any impact in Pharmacokinetic & statistical analysis? FDA may raises a question about the measurement of true Cmax because of insufficient early sampling times. FDA Guidance states that collection of an early time point between 5 and 15 minutes after dosing followed by additional sample collections (e.g., two to five) in the first hour after dosing may be sufficient to assess early peak concentrations. If this sampling approach is followed, FDA recommends that data sets be considered adequate, even when the highest observed concentration occurs at the first time point. In your case, since the above sampling approach is not followed, FDA may raise on observation. — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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lukamar ☆ Poland, 2012-09-10 15:54 (4625 d 05:15 ago) @ auditor Posting: # 9166 Views: 7,835 |
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❝ Kindly give your suggestion about how the agency will take this issue and is it affect the study? Any agency may question reliability of Cmax assessment in such case. And they often do. The only way to see whether this affects the study, is to recalculate study results with all subjects with Cmax at first time point excluded. If your recalculated results remains within acceptance criteria then you can state that Cmaxes at first time point had no impact on study conclusions. If however these results don't show bioequivalence, there is great risk of study rejection. Especially if there was possibility of including additional, early blood samples. And there was as you're saying about first sample at 0.5h. Literature data of Cmax starting with 1 hour will rather not help you. Your sampling scheme was not adequate for proper Cmax characterization in this study - whether it was justifed at the time of study planing or was not, is secondary in this case. This is what I can say from my experience with EU agencies. Best regards, Lukas |
Ing. Helmut Schütz