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nermina ☆ Bosnia and Herzegovina, 2010-01-15 16:27 (6003 d 23:33 ago) Posting: # 4608 Views: 9,342 |
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Hello, does anyone have experience with tramadol BE study, precisely is it necessary for granting MA in EU to determinate in BE study the parent drug and metabolite M1, or just the parent drug. Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2010-01-15 17:08 (6003 d 22:52 ago) @ nermina Posting: # 4609 Views: 8,059 |
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— 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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nermina ☆ Bosnia and Herzegovina, 2010-01-15 17:15 (6003 d 22:45 ago) @ Helmut Posting: # 4610 Views: 8,191 |
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Thanks for a prompt answer. I saw on web of UK regulatory agency (www.mhra.gov.uk) in Public assessment report, that they've required a determination of M1 metabolite too. That confused me. Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
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Helmut ★★★ Vienna, Austria, 2010-01-15 17:40 (6003 d 22:20 ago) @ nermina Posting: # 4611 Views: 8,110 |
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Dear Nermina! ❝ I saw on web of UK regulatory agency in Public assessment report, that they've required a determination of M1 metabolite too. Interesting. Can you give us a direct link to the document (I'm not in the mood of searching). — 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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mvgchakravarthi ☆ India, 2010-01-18 16:19 (6000 d 23:40 ago) @ Helmut Posting: # 4613 Views: 7,969 |
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Dear Nermina As per FDA BE guidance document, need to estimate parent "Tramadol" only but not metabolite. Regards M.V.G.Chakravarthi Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
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Helmut ★★★ Vienna, Austria, 2010-01-18 16:44 (6000 d 23:16 ago) @ mvgchakravarthi Posting: # 4614 Views: 8,039 |
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Dear M.V.G.Chakravarthi, have you read the entire thread? The application is for the EU, not for the USA. — 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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raghu ★ India, 2010-01-20 18:53 (5998 d 21:06 ago) @ Helmut Posting: # 4625 Views: 8,010 |
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Dear Nermina, If an active metabolite is available and it is quantifiable in biological fluid (i.e plasma, urine etc), better to analyse and submit as a supportive evidence. It may add some additional cost, but it is safer. Nowadays, Sponsor's initially submit the ANDA submission to the proposed countries (EU), Later on they might submit to the rest of the world. If any query comes after several years, then it would be difficult to answer and product approval may be questionable ??? Regards Raghavender Chenna  |
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Helmut ★★★ Vienna, Austria, 2010-01-20 19:18 (5998 d 20:41 ago) @ raghu Posting: # 4626 Views: 8,185 |
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Dear Raghavender! ❝ Nowadays, Sponsor's initially submit the ANDA submission to the proposed countries (EU), In the EU the sponsor applies for Market Authorization (MA) - ANDA is FDA's term.  ❝ Later on they might submit to the rest of the world. Well, except to the FDA (unless you have included FDA's RLD in a 3way-study). Some countries except the European reference product if it can be demonstrated that the reference product in that particular country is similar (based on in vitro data), whilst other require the innovators product marketed in their country as a reference anyhow. This was the driving force behind WHO's 'International Comparator' - but I'm afraid it didn't work out. ❝ If any query comes after several years, then it would be difficult to answer and product approval may be questionable ??? You are right. — 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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ratna ☆ 2010-01-21 07:36 (5998 d 08:23 ago) @ Helmut Posting: # 4635 Views: 8,209 |
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Dear HS, ❝ Interesting. Can you give us a direct link to the document (I'm not in the mood of searching). Here is the Public assessment report of Tramadol. Regards, Ratna Edit: THX! Document linked. [Helmut] |
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Otto ● 2010-01-25 14:26 (5994 d 01:34 ago) @ nermina Posting: # 4645 Views: 8,165 |
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I worked with Tramadol in the past. Since M1 is the active metabolite that's mainly responsible for the efficacy of Tramadol (strong afinity to the µ-receptor) it is necessary to show BE also for M1. I would be surprised if a study without the BE for M1 would be accepted. Regards, Otto |
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Helmut ★★★ Vienna, Austria, 2010-02-07 18:01 (5980 d 21:58 ago) @ Otto Posting: # 4726 Views: 7,950 |
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Dear Otto! ❝ Since M1 is the active metabolite that's mainly responsible for the efficacy of Tramadol (strong afinity to the µ-receptor) it is necessary to show BE also for M1. I would be surprised if a study without the BE for M1 would be accepted. Well, this point of view has clearly shifted from BE seen as surrogate of Therapeutic Equivalence towards a measure of Pharmaceutical Quality (the 'human testtube'-approach) in the past years. See the new BE-guideline (Section 4.1.5 Characteristics to be investigated / Parent compound or metabolites): In principle, evaluation of bioequivalence should be based upon measured concentrations of the parent compound. The reason for this is that Cmax of a parent compound is usually more sensitive to detect differences between formulations in absorption rate than Cmax of a metabolite. [...]
— 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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kumarnaidu ★ Mumbai, India, 2014-03-15 12:36 (4484 d 03:24 ago) @ Helmut Posting: # 12634 Views: 6,607 |
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Dear All, We have submitted old tramadol study recently in EU that was conducted as per the old EMA GL. As per the current GL, for establishing BE we have to consider enantiomers of tramadol and its active metabolite. And hence we have recieved the following query from the agency asking the same. The use of an achiral bioanalytical method for tramadol and its metabolite should be discussed and justified. Can anyone help me out to defend this ?  — Kumar Naidu |
Ing. Helmut Schütz