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hiren379 ★ India, 2012-08-14 14:01 (5061 d 09:27 ago) Posting: # 9060 Views: 5,754 |
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Hello all, How to prove that there is no high variability in Distribution and Clearance phase for using truncated AUC approach for USFDA? |
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Helmut ★★★   Vienna, Austria, 2012-08-14 16:18 (5061 d 07:10 ago) @ hiren379 Posting: # 9061 Views: 4,875 |
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Dear Hiren! ❝ How to prove that there is no high variability in Distribution and Clearance phase for using truncated AUC approach for USFDA? Very good question! I was always wondering myself what is the rationale behind this statement in FDA’s guidance (contrary to EMA’s where truncation is acceptable for all IR products). One could only prove lacking high variability in distribution and clearance (CVintra <30%) by administering a solution (!) twice. Since this variability is expected to be less than the variability seen after administration of a formulation, maybe reference to literature data or previous studies (where CVintra was <30%) is sufficient as well. Does anybody have some practical experiences? P.S.: Do you have an answer to my question at the end of this post? — 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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hiren379 ★ India, 2012-08-14 16:54 (5061 d 06:35 ago) @ Helmut Posting: # 9063 Views: 4,778 |
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Thanks HS, What shall be the parameters for the same.. I guess Cl for clearance and Vd for volume of distribution...correct me if wrong or any more PK metrices.... |
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Helmut ★★★ Vienna, Austria, 2012-08-14 17:22 (5061 d 06:06 ago) @ hiren379 Posting: # 9064 Views: 4,844 |
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Hi Hiren! ❝ What shall be the parameters for the same.. ❝ I guess Cl for clearance and Vd for volume of distribution...correct me if wrong or any more PK metrices.... CL and V are not accessible after an extravascular dose since the fraction absorbed is unknown. One gets only CL/f and V/f. FDA is interested in variability, not an CI. IMHO CVintra of AUC∞ <30% would be of interest. — 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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hiren379 ★ India, 2013-12-13 08:53 (4575 d 13:35 ago) @ Helmut Posting: # 12051 Views: 3,947 |
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Hello HS, I have a question here Will high intra-subject variability in Clearance and distribution have any role when Parallel design with truncation approach is implemented  Will FDA ask to demonstrate low intra-subject variability in parallel design also What is the rationale for using intra-subject variability in parallel design approach? |
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Dr_Dan ★★ Germany, 2013-12-13 10:49 (4575 d 11:39 ago) @ hiren379 Posting: # 12054 Views: 3,950 |
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Dear hiren379 If you use a parallel design you will not have an intra-individual i.e. within subject comparison of test and reference and consequently you will not be able to assess any intra-subject variability. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
Ing. Helmut Schütz