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achintparikh ☆ India, 2012-06-15 10:23 (5125 d 00:25 ago) Posting: # 8741 Views: 7,042 |
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Dear All I need suggestion and reference for food and posture restriction criteria for steady state studies (Europe) of drug formulation (modified release) administered twice daily (12 hourly) What about the minimum fasting i.e. 8 hours predose and 4 hours post dose for second dose i.e. 12 hours after first (morning) dose. Have a Great Day!!! Pradeep Labana |
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Helmut ★★★   Vienna, Austria, 2012-06-15 19:50 (5124 d 14:59 ago) @ achintparikh Posting: # 8746 Views: 6,344 |
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Dear Pradeep! Please follow common sense. If you dose at 07:00 and 19:00 and follow the -8h/+4h fasting restriction per dose you would end up with the last meal 23:00 before administration and the first one 23:00 on the profile day. Have never seen such a study. The -8h restriction is not applicable to the second dose; the +4h restriction is at least debatable. BTW, you were referring to the IR GL (2010); the MR NfG (1999) does not contain such a statement at all. — 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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achintparikh ☆ India, 2012-06-16 08:42 (5124 d 02:06 ago) @ Helmut Posting: # 8747 Views: 6,178 |
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Dear Helmut Thanks for your suggestion. We have used the same design. But we are in search of the reference for second dose pre and post dose diet restriction. Pradeep Labana |
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drgunasakaran1 ★★  2012-06-16 09:25 (5124 d 01:24 ago) @ achintparikh Posting: # 8748 Views: 6,191 |
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❝ But we are in search of the reference for second dose pre and post dose diet restriction. Dear Mr Pradeep Labana, EMA does not specify about fasting criteria for Evening dose and Evening post dose restrictions period in their Bioequivalence Guidance. Practically, it is not possible and feasible to maintain the same 08 hours fasting criteria and 04 hours post dose food restriction after evening dose in case of Multiple dose studies. Whereas, FDA's Old BE Guidance states that "The evening dose should be administered after a fast of at least 2 hours and subjects should continue fasting for 2 hours post-dose" and CDSCO's BE Guidance also states that "For multiple dose fasting studies, when a evening dose must be given, two hours of fasting before and after the dose is considered acceptable". You can maintain the same 02 hours fasting prior to evening dose and 02 hrs post dose fasting criteria after the Evening dose for EMA submission which will be generally acceptable. — 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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Chiku ☆ India, 2012-06-18 14:09 (5121 d 20:40 ago) @ achintparikh Posting: # 8768 Views: 6,188 |
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Dear all, As per this document (16 February 2012 EMA/618604/2008 Rev. 4 Committee for Human Medicinal Products (CHMP)) page no 6: "3. MR formulations developed as generics For generic products, the guideline recommends two single dose 2 way crossover studies evaluating test and reference fasted, and test and reference fed, respectively. Alternatively a single dose 4 way crossover study (MR generic fed and fasted + reference fed and fasted) can be conducted to demonstrate bioequivalence between generic and reference in both fasting and fed state. In a 4 way crossover study a comparison of the food effect for test and reference is possible, which will not be the case if two 2 way cross over studies are conducted, as between study comparison of food effect is not recommended." Does this mean only Fasting and Fed is required for MR or we should follow NfG 1999 where Fasting fed and Steady state is recommended. Any idea when will MR guideline BE studies be published? Regards, CHiku Edit: Q&A document linked. [Helmut] |
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Helmut ★★★ Vienna, Austria, 2012-06-18 15:01 (5121 d 19:48 ago) @ Chiku Posting: # 8769 Views: 6,278 |
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Dear Chiku! ❝ Does this mean only Fasting and Fed is required for MR or we should follow NfG 1999 where Fasting fed and Steady state is recommended. The Q&A document quoted the 1999 MR NfG (Appendix I, 2-way cross-over studies: Tfasting/Rfasting and Tfed/Rfed). Inline with the IR GL (2010) a 4-way cross-over is now an acceptable alternative design (In cases where information is required in both the fed and fasted states, it is acceptable to conduct either two separate two-way cross-over studies or a four-way cross-over study.). Nothing has changed concerning the recommendation (fed + fasting). A clarification was made concerning a “suspected non-linear food effect”: For both single-unit formulations and multiple-unit formulations, the highest strength should in general be studied. In case a non-linearity in the food effect is suspected, the food interaction study should be performed with the highest and the lowest strength. Steady state is still recommended. On a case-to-case basis this requirement was waived in the past (some delayed / multiphasic / pulsatile release formulation with essentially no accumulation). Might ‘make it’ to the MR GL draft, but I’m not too optimistic.
❝ Any idea when will MR guideline BE studies be published? According to conversations with members of the PK group I had in Budapest two weeks ago end of QIII/2012. — 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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Chiku ☆ India, 2012-06-19 07:45 (5121 d 03:04 ago) @ Helmut Posting: # 8785 Views: 6,041 |
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Dear HS, Thank you very much for clarification.... Regards, Chiku |
Ing. Helmut Schütz