Log in
Register|
wxp ☆ China, 2013-03-21 16:38 (4844 d 04:50 ago) Posting: # 10253 Views: 6,004 |
|
|
Dear all, I wonder how to confirm a highly variable drug? I tried to find a highly variable drug list or table, but I did not find one. I also searched the drug (e.g., simvastatin or metformin) on the FDA's website. But I could not find a direct conclusion. Could anyone give me some advice to confirm a highly variable drug? By reading literatures? — Best regards, Xipei China |
|
ElMaestro ★★★ Denmark, 2013-03-21 17:07 (4844 d 04:20 ago) @ wxp Posting: # 10254 Views: 5,052 |
|
|
Hi wxp, ❝ I wonder how to confirm a highly variable drug? For EU and US submissions the safe route is not just literature. If you conduct a study and conduct it well and with an appropriate design, and the intra-CV is >30% then you have reached the goal. Some member or other may chime in with the distinction between drug and drug product. — Pass or fail! ElMaestro |
|
wxp ☆ China, 2013-03-22 02:58 (4843 d 18:29 ago) (edited on 2013-03-22 10:17) @ ElMaestro Posting: # 10258 Views: 5,005 |
|
|
Hi ElMaestro, I agree with the way you mentioned. But it is time-consuming and needs more money.We did a 2×2 bioequivalance study of simvastin in 24 healthy volunteers. The intra-CV was >30%, which demonstrated that the sample size was not enough for a HV drug. I think if we can confirm a drug a HV drug before the study design, it will save a lot of time and money. Best regards, Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe] — Best regards, Xipei China |
|
ElMaestro ★★★ Denmark, 2013-03-22 11:33 (4843 d 09:55 ago) @ wxp Posting: # 10262 Views: 4,952 |
|
|
Hi wxp, ❝ I agree with the way you mentioned. But it is time-consuming and needs more money.We did a 2×2 bioequivalance study of simvastin in 24 healthy volunteers.The intra-CV was >30%, which demonstrated that the sample size was not enough for a HV drug. I think if we can confirm a drug a HV drug before the study design, it will save a lot of time and money. You are right to say if you could confirm that a drug is HV before the trial pivotal trial then things would be cheaper, faster, easier. But at the end of the day that's not really widely acceptable in countries like EU and USA. If company X has a formulation which in a study displayed HV (now I am talking a HV drug product) then this does not per se mean that a formulation with the same API from company Y is also displaying HV. The topic has been thoroughly discussed at various levels at the agencies. I believe you need to show HV for your formulation if you want to claim HV for it. — Pass or fail! ElMaestro |
|
d_labes ★★★ Berlin, Germany, 2013-03-23 16:37 (4842 d 04:51 ago) @ ElMaestro Posting: # 10266 Views: 4,942 |
|
|
Dear ElMaestro, ❝ The topic has been thoroughly discussed at various levels at the agencies. I believe you need to show HV for your formulation if you want to claim HV for it. The regulatory agencies are not interested in showing HV for the Test formulation. The only thing you have to show is that the Reference variability has CV > 30%. — Regards, Detlew |
|
wxp ☆ China, 2013-03-25 15:24 (4840 d 06:03 ago) @ d_labes Posting: # 10274 Views: 4,902 |
|
|
❝ The regulatory agencies are not interested in showing HV for the Test formulation. The only thing you have to show is that the Reference variability has CV > 30%. Thank you, d_labes. Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] — Best regards, Xipei China |
|
Helmut ★★★   Vienna, Austria, 2013-03-23 18:35 (4842 d 02:52 ago) @ ElMaestro Posting: # 10268 Views: 5,081 |
|
|
Hi wxp & ElMaestro, ❝ […] Some member or other may chime in with the distinction between drug and drug product. HVD: CVW of a solution ≥30%.HVDP: CVW of a formulation ≥30%.In both cases replicate administrations are required. My favorite example: Some gastric resistant formulations of diclofenac are HVDPs, practically all topical formulations are HVDPs – whereas diclofenac itself is not a HVD (CVintra of a solution ~8%). — 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 |
|
wxp ☆ China, 2013-03-25 15:20 (4840 d 06:08 ago) @ Helmut Posting: # 10273 Views: 4,946 |
|
|
❝ ❝ ❝ ... Thank ElMaestro and Helmut! I have a further understanding of HVD. As far as I understand, if we are not sure whether a drug is HVD, a pilot clinical trial is needed to investigate the within-subject variability. — Best regards, Xipei China |
Ing. Helmut Schütz