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sam ★ India, 2012-09-28 15:28 (4589 d 22:17 ago) Posting: # 9273 Views: 9,174 |
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Dear All, I wanted to do the IVIVC of few formulations and I have with me the invitro data of the formulation at different pH like 1.2, 6.5 and 7.4. I have also invivo data. I am handling the IVIVC toolkit for doing the IVIVC. Now plz suggest me which data i have to select as fast relaese and slow release data and secondly which data will be considered as internal validation and external validation data. I have gone through the examples and manual guidance of the winnonlin. From there I did practice on their provided data. But I am bit confused that which data I have to select for the internal validation and which data for external validation from my invitro data of different pH. In the example guide it has been written as
Edit: Category and subject line changed. [Helmut] |
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jag009 ★★★ NJ, 2012-10-01 19:41 (4586 d 18:04 ago) (edited on 2012-10-01 22:32) @ sam Posting: # 9291 Views: 8,212 |
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Hi Sam,
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sam ★ India, 2012-10-03 11:18 (4585 d 02:27 ago) @ jag009 Posting: # 9302 Views: 8,207 |
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Dear John Thanks for your esteemed reply. I have three batches with invitro data and one invivo data batches. I have IR profile to generate UIR. I want to generate the IVIVC for the formulations with different strength. Let see I have the data for 10mg and based on that data I want the Biowaiver for 5mg data by IVIVC. |
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jag009 ★★★ NJ, 2012-10-03 18:06 (4584 d 19:39 ago) @ sam Posting: # 9304 Views: 8,095 |
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Hi Sam, You need in-vivo data for each of the three batches. You want to claim biowaiver on the lower strength (5mg) with an IVIVC from 10mg? I don't think that is acceptable (not sure but others might have experience in this aspect). John |
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Helmut ★★★   Vienna, Austria, 2012-10-03 18:13 (4584 d 19:32 ago) @ jag009 Posting: # 9305 Views: 8,225 |
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Hi John & Sam, ❝ You want to claim biowaiver on the lower strength (5mg) with an IVIVC from 10mg? I don't think that is acceptable (not sure but others might have experience in this aspect). No, that’s not acceptable. IVIVC is only applicable to MR formulations with identical strengths. A proportionality-based biowaiver is a different cup of tea. — 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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Helmut ★★★ Vienna, Austria, 2012-10-03 17:46 (4584 d 19:58 ago) @ sam Posting: # 9303 Views: 8,142 |
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Dear Sam! ❝ I have gone through the examples and manual guidance of the winnonlin. From there I did practice on their provided data. But I am bit confused … Consider registering at Pharsight’s Extranet and post your question there. ❝ I have three batches with invitro data and one invivo data batches. ❝ I have IR profile to generate UIR. To establish an IVIVC you need in vivo data for all (!) batches. This seems not to be case. As Jean Michel always preaches, start with in vivo and then (!) try to find in vitro conditions which are discriminatory/predictive. If your dissolution medium is Earl Grey tea with milk and sugar, fine. — 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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sam ★ India, 2012-10-04 14:08 (4583 d 23:37 ago) @ Helmut Posting: # 9306 Views: 8,039 |
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Dear Helmut, Thanks for your immediate response. I have one more query that plz let me know that what are the criteria for selection of the Internal Validation, External Validation and Target Batches. Among the batches which batch I have to drag for the Internal Validation. As per the IVIVC manual drag “CR01, CR02, and then CR04 from the Formulations list to the Internal Validation field”. But I am bit confused how they have selected these batches for the Internal Validation. Again the same query for the External Validation that which batch I have to select for External Validation. As per the manual they have selected CR03 for the External Validation field. And which batch will be the Target Batch field. Hope you understand the fact. As I am in the beginning and unable to drag my formulation batches to the specific fields. I don’t know the criteria for their selection. |
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Helmut ★★★ Vienna, Austria, 2012-10-04 16:17 (4583 d 21:28 ago) @ sam Posting: # 9308 Views: 7,980 |
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Dear Sam! ❝ As per the IVIVC manual drag “CR01, CR02, and then CR04 from the Formulations list to the Internal Validation field”. But I am bit confused how they have selected these batches for the Internal Validation. This is just an example; ask Pharsight why the have named the formulations as such. They did not select anything – these are artificial data. IVIVC_Vivo_Subj.CSV contains data of 25 subjects each. CR01–CR04 are increasingly slower releasing, IV and IR are self-explanatory. Targ has release characteristics similar to CR03.❝ Again the same query for the External Validation that which batch I have to select for External Validation. As per the manual they have selected CR03 for the External Validation field. So what? ❝ And which batch will be the Target Batch field. What about Targ?❝ Hope you understand the fact. No, I don’t see the problem. Why don’t you ask at Pharsight’s Extranet as suggested? ❝ As I am in the beginning and unable to drag my formulation batches to the specific fields. Did you map IVIVC_Vivo_Subj.CSV to the IVIVC-object? In Setup navigate to InVivoData and drag IVIVC_Vivo_Subj.CSV to Mappings.❝ I don’t know the criteria for their selection. See above. If you fail reproducing the manual’s example(s) consider attending one of Pharsight’s training courses. There is also a basic IVIVC training in Mumbai (1–2 December). — 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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jag009 ★★★ NJ, 2012-10-04 18:10 (4583 d 19:35 ago) (edited on 2012-10-04 20:09) @ sam Posting: # 9309 Views: 8,015 |
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Hi Sam, Don't bother with how Pharsight selects CR01, CR02, CR03, CR04 for their IVIVC example... It is just an example. Target formulation is your target formulation, you know... Formulation which is bioequivalent to the reference (for ANDA). In short, internal validation means to determine the predictability of the IVIVC model by testing it with data that was used in its development: The Fast, Medium, slow formulation data. External validation means you use data from a formulation which is not involved in developing the IVIVC model to test the IVIVC model for its predictability. In both validation, the predictability is to compare the IVIVC predicted in-vivo profile to the observed (real data) in-vivo profile. Comparison is based on AUC and Cmax. Refer to FDA guidance for predictability formula and criteria. See if you can get access to a book "In-vitro In-vivo correlatons" written by Young, Devane and Butler. Read that book and you will have all your answers. Almost forgot, Pharsight gives online webinar demonstration of their IVIVC software. Contact Pharsight for their next demo and you will get most of your answers there. John |
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sam ★ India, 2012-10-05 09:32 (4583 d 04:13 ago) @ jag009 Posting: # 9312 Views: 7,945 |
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Dear John Thanks for your useful explanations related to the selection of the internal, external and target batches. If I understand you in right way then I think that Target formulation is the previously approved formulation or the formulation for which I have to show the bioequivalent to the reference (for ANDA). As far as the internal validation is concerned I am clear that these are the formulations which are required to establish the IVIVC model. Means the data of three batches of formulation (slow, medium and fast) in invtro as well invivo conditions. For the External validation the data from a formulation which will be not involved in developing the IVIVC model to test the IVIVC model for its predictability. So tell me from where I can this data, means I have to run this separate batch or I can the data from internet. Hope for the positive reply |
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jag009 ★★★ NJ, 2012-10-06 00:51 (4582 d 12:53 ago) @ sam Posting: # 9322 Views: 7,921 |
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Hi Sam ❝ If I understand you in right way then I think that Target formulation is the previously approved formulation or the formulation for which I have to show the bioequivalent to the reference (for ANDA). Correct ❝ For the External validation the data from a formulation which will be not involved in developing the IVIVC model to test the IVIVC model for its predictability. So tell me from where I can this data, means I have to run this separate batch or I can the data from internet. Yes, meaning you need another batch. You can't just grab something from the internet. For example, you vary the coating (alter the release rate) to generate 4 formulations, 3 of them you use for IVIVC, the 4th one for validation. From the book, "The ideal situation is that the formulations not used in the model development should be different enough in release rate to appropriately evalute the predictability of the model."1 1. Young D, Devane JG, Butler J. In Vitro-In VIvo Corrlations. Advance in Experimental and Medicine and Biology, Vol 423, page 89. John |
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Helmut ★★★ Vienna, Austria, 2012-10-06 03:23 (4582 d 10:21 ago) @ jag009 Posting: # 9326 Views: 7,993 |
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— 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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jag009 ★★★ NJ, 2012-10-08 20:13 (4579 d 17:32 ago) @ Helmut Posting: # 9341 Views: 7,842 |
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Ok Boss  |
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Helmut ★★★ Vienna, Austria, 2012-10-08 21:19 (4579 d 16:26 ago) @ jag009 Posting: # 9344 Views: 7,830 |
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Hi John, go ahead if you want. I’m nobody’s boss (literally). But I reckon the both of us got caught in a trap.  — 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 |
Ing. Helmut Schütz