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Helmut ★★★   Vienna, Austria, 2012-03-14 17:03 (5218 d 20:12 ago) Posting: # 8273 Views: 5,214 |
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Dear all, does anybody have experiences with BE studies in Russia? According to “Lex Putin” BE studies have to be conducted in Russia – foreign data are not accepted. Interesting (2008 GL):
During bioequivalence estimation it is possible that data of one or several participants have much different parameters comparing to rest of the group – so called outliers. Outliers detection is made by special statistical analyses. For demonstration of such observations diagrams of individual standardized differences are presented (centralized for mean values and normalized for standard deviation). In Appendix 4 it is stated: Common plan of a bioequivalence study:
— 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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Vasily ☆ Moscow, 2012-03-15 13:50 (5217 d 23:24 ago) @ Helmut Posting: # 8276 Views: 4,497 |
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Dear HS, To the best of my knowledge 2008 GLs are not cited in what you call "Lex Putin" (federal law #61) and thus can be treated only as recommendations. So theoretically your BE study protocol can be approved even if your sampling exceeds 200ml. Regards, Vasily — Sincerely, Vasily |
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Helmut ★★★ Vienna, Austria, 2012-03-15 14:46 (5217 d 22:29 ago) @ Vasily Posting: # 8277 Views: 4,569 |
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Dear Vasily, THX for your valuable insider’s information! ❝ To the best of my knowledge 2008 GLs are not cited in what you call "Lex Putin" (federal law #61) and thus can be treated only as recommendations. Agree; guidelines are only some kind “soft law”. It always depends on the IEC’s and agency’s point of view on how strict they have to be followed.  ❝ So theoretically your BE study protocol can be approved even if your sampling exceeds 200ml. Do you have any practical experiences with higher volumes? BTW, since the guideline only mentions 2×2 cross-overs how to you deal with drugs with long-half lives or studies in patients with unstable diseases (only parallel design feasible in both cases)? — 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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Vasily ☆ Moscow, 2012-03-15 16:25 (5217 d 20:50 ago) @ Helmut Posting: # 8278 Views: 4,567 |
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Dear Helmut, ❝ THX for your valuable insider’s information! I can hardly be treated as insider since I am not related to Russian regulatory in any way (however I live inside Russia, so that might qualify me as a Russian insider )❝ Agree; guidelines are only some kind “soft law”. It always depends on the IEC’s and agency’s point of view on how strict they have to be followed. Unfortunately it is very difficult and time consuming to get official response in paper clarifying agency's view so you usually can test the system only by submitting your protocol. (i must admit that once we managed to receive pre-submission agency's recommendations for our novel cardioplegic solution. Recommendations included suggestion to test the possible effect of our solution on the ability to drive. I treasure this letter and re-read it on my bad days )❝ Do you have any practical experiences with higher volumes? BTW, since the guideline only mentions 2×2 cross-overs how to you deal with drugs with long-half lives or studies in patients with unstable diseases (only parallel design feasible in both cases)? No practical experience with higher doses in BE sofar. ❝ BTW, since the guideline only mentions 2×2 cross-overs how to you deal with drugs with long-half lives or studies in patients with unstable diseases (only parallel design feasible in both cases)? Parallel design is allowed. I know that parallel BE study in glaucoma patients (sponsored by E. European company) was recently approved. — Sincerely, Vasily |
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Helmut ★★★ Vienna, Austria, 2012-03-15 16:46 (5217 d 20:29 ago) @ Vasily Posting: # 8279 Views: 4,486 |
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Dear Vasily! ❝ I can hardly be treated as insider since I am not related to Russian regulatory in any way (however I live inside Russia, so that might qualify me as a Russian insider Perfect qualification! I’m not related to any Agency as well, but feel qualified enough to dabble in a lot of stuff here.  ❝ Unfortunately it is very difficult and time consuming to get official response in paper clarifying agency's view so you usually can test the system only by submitting your protocol. Same procedure as everywhere. Even if you go for an advisory meeting recommendations are non-binding – both for the agency and the sponsor. ❝ i must admit that once we managed to receive pre-submission agency's recommendations for our novel cardioplegic solution. Recommendations included suggestion to test the possible effect of our solution on the ability to drive. That’s a nice one! ❝ ❝ BTW, since the guideline only mentions 2×2 cross-overs how to you deal with drugs with long-half lives or studies in patients with unstable diseases (only parallel design feasible in both cases)? ❝ ❝ Parallel design is allowed. I know that parallel BE study in glaucoma patients (sponsored by E. European company) was recently approved. Good to hear. Makes sense. — 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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ElMaestro ★★★ Denmark, 2012-03-16 14:22 (5216 d 22:53 ago) @ Helmut Posting: # 8284 Views: 4,442 |
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Hi HS, ❝ (...) I’m surprised by the limited sampling volume. Might require (at least) partial revalidation (lower sample volume, higher LLOQ, or even development of an improved method). Yes, that's a good idea. In practice you might find that some of the principles used in 'our' part of the world do not always apply or are not always necessary in Russia. Some of the state-of-the-art thinking today is founded in GCP and GLP, which are only pseudo-quasi-adopted in Russia. One often freezes two aliquots per subjects per sample point. You might argue that although GCP/GLP does not really explicitly say "freeze two aliquots or get a citation!", the reason for freezing two aliquots is nevertheless often a GCP/GLP consideration which can prove extremely helpful just in case... So in Russia you might easily get by using just one aliquot, and that means you need to sample only half the amount of blood you'd be inclined to take elsewhere. And then, of course, light a candle in the church and pray the just-in-case scenarios are and remain free fantasy. — Pass or fail! ElMaestro |
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Helmut ★★★ Vienna, Austria, 2012-03-16 14:44 (5216 d 22:30 ago) @ ElMaestro Posting: # 8285 Views: 4,443 |
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Dear ElMaestro! ❝ One often freezes two aliquots per subjects per sample point. You might argue that although GCP/GLP does not really explicitly say "freeze two aliquots or get a citation!", the reason for freezing two aliquots is nevertheless often a GCP/GLP consideration which can prove extremely helpful just in case... ![[image]](img/uploaded/image28.png) ❝ So in Russia you might easily get by using just one aliquot, and that means you need to sample only half the amount of blood you'd be inclined to take elsewhere. And then, of course, light a candle in the church and pray the just-in-case scenarios are and remain free fantasy. Yep. On the other hand the two-aliquot business was mainly introduced to be protected against sample-loss during shipment (stuck in US-customs until all dry ice evaporates, plane crash, meteorite fall, …) Since everything has to be performed in Russia, go for a full service provider (clinical + analytical) or at least two different ones of close proximity. BTW, the three freeze-thaw-cycles were developed in times where nobody used aliquotes but TEF 1–3*.
— 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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