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london12 ● 2009-08-25 16:21 (5527 d 13:44 ago) Posting: # 4110 Views: 4,967 |
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Dear all Hope you can help me out. I am planning to repeat a fasted bioequivalence study for a particular product. Previously two studies have been performed using crystalline API, one fed study and one fasted. The fed study passed but the fasted study passed in that sense that it was within protocol-defined wider criteria. The wider criteria was not accepted by some authorities and therefore the fasted study will be repeated. I have available tablet batches manufactured using different source of API, ie amorphous material. What is your opinion regarding conducting fed and fasted studies for the same product using different forms of active? Dissolution profiles are similar in all cases but there was a minor change in the target coating amount (the coating is critical). Best regards london12 |
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Helmut ★★★   Vienna, Austria, 2009-08-27 02:44 (5526 d 03:21 ago) @ london12 Posting: # 4122 Views: 4,293 |
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Dear London and some numbers (you know this note for sure; consider adding a signature to your profile)… In the following I changed the order of your post to help myself in tackling the problem. ❝ […] one fed study and one fasted. Let me guess: a modified release formulation, probably delayed, gastric resistant? ❝ The fed study passed but the fasted study passed in that sense that it was within protocol-defined wider criteria. EU (NfG 2001 or earlier) or a country following closely EU's guidelines in their national ones? ❝ The wider criteria was not accepted by some authorities and therefore […] Yes, the 2006 Q&A-document… ❝ […] the fasted study will be repeated. Danger! I would say that the part about mandatory submission of all studies from the 2008 BE drafted guideline will survive and make it to the final version. No good idea to come up with two studies, one was not BE (even if just underpowered for the conventional 0.8–1.25) and another one was… See also this post. ❝ […] studies have been performed using crystalline API […] ❝ […] I have available tablet batches manufactured using different source of API, ie amorphous material. What is your opinion regarding conducting❝ fed and fasted studies for the same product using different forms of active? Hhm, I wouldn't call such a change of the API a minor one. The only exception I can think of is an API with very high solubility (within BCS I or III). If your product is an MR, forget biowaivers. There are quite nasty examples in the literature of bioinequivalence when the API was changed from microcrystalline to amorphous. Just think about phenytoin intoxications in the late 1970s. ❝ Dissolution profiles are similar in all cases but there was a minor change in the target coating amount (the coating is critical). More infos, please. Is it a modified release formulation (maybe an IVIVC may help) or just another *prazole?— 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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Ohlbe ★★★ France, 2009-08-31 03:34 (5522 d 02:31 ago) @ Helmut Posting: # 4137 Views: 4,116 |
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Dear London and Helmut, ❝ ❝ [...] the fasted study will be repeated. ❝ ❝ Danger! I would say that the part about mandatory submission of all studies from the 2008 BE drafted guideline will survive and make it to the final version. Independently of the guideline, for EU submissions Annex I to Directive 2001/83/EC, as amended by Directive 2003/63/EC, requires that all clinical trials conducted on the product be submitted, whether positive or negative. A lot of fuss has been made about this paragraph in the draft EU guideline. There was nothing new in it: this requirement is in place since at least 1975 (Annex to Directive 75/318/EC). Regards Ohlbe |
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Helmut ★★★ Vienna, Austria, 2009-08-31 17:36 (5521 d 12:29 ago) @ Ohlbe Posting: # 4138 Views: 4,163 |
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Dear Ohlbe! ❝ Independently of the guideline, for EU submissions Annex I to Directive 2001/83/EC, as amended by Directive 2003/63/EC, requires that all clinical trials conducted on the product be submitted, whether positive or negative. ❝ ❝ A lot of fuss has been made about this paragraph in the draft EU guideline. There was nothing new in it: this requirement is in place since at least 1975 (Annex to Directive 75/318/EC). Thanks for the information. I didn't know that! In those ol' days when faxmachines used fanfold thermoprint paper, I was pretty sure that when I was transmitting a 'not-so-nice' drafted report to the sponsor on their side the fax went straight into a document shredder - and the final report to a filing cabinet in the third basement and never saw daylight again... P.S.: 75/318/EC, Annex I to 2001/83/EC, Annex I to 2003/63/EC. — 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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qualityassurance ★ 2023-08-03 12:44 (436 d 17:21 ago) @ Helmut Posting: # 23692 Views: 1,962 |
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Dear Helmunt, ❝ There are quite nasty examples in the literature of bioinequivalence when the API was changed from microcrystalline to amorphous. Thanks and regards, QA |
Ing. Helmut Schütz