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PVRC ☆ India, 2021-05-10 20:12 (1310 d 19:37 ago) Posting: # 22338 Views: 3,521 |
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Hi all, For one of the product, the agency recommend to demonstrate comparative PK in the absence of bioequivalence. The question is that whether all bioequivalence criteria (like 80-125%, group effect etc.,) are still applicable to demonstrate comparative PK. Thanks in advance.... |
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Helmut ★★★   Vienna, Austria, 2021-05-12 13:25 (1309 d 02:24 ago) @ PVRC Posting: # 22345 Views: 2,847 |
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Hi PVRC, ❝ […] the agency … May I ask: Which agency? ❝ … recommend to demonstrate comparative PK in the absence of bioequivalence. Do I get you right: The study was planned to demonstrate BE, failed, and now you were asked about ‘comparative PK’? I never came across such a term. ❝ The question is that whether all bioequivalence criteria (like 80-125%, group effect etc.,) are still applicable to demonstrate comparative PK. PK means commonly modeling, which is not acceptable in BE (only NCA). That’s for good reasons (results depend on the chosen model, software/version, initial estimates, parameter constraints, convergence criteria, PopPK or two-stage approach,  ). Hence, the outcome is not necessarily reproducible.When you decide to dive into this murky water, you will be surprised. Even for a simple one-compartment model I bet you will get a huge variability in the absorption rate constant. IMHO, 80–125% will practically never work. — 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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PVRC ☆ India, 2021-05-12 17:48 (1308 d 22:00 ago) @ Helmut Posting: # 22346 Views: 2,875 |
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Hi Helmut, Thank you for the reply.., ❝ ❝ […] the agency … ❝ ❝ May I ask: Which agency? The FDA ❝ … recommend to demonstrate comparative PK in the absence of bioequivalence. ❝ ❝ Do I get you right: The study was planned to demonstrate BE, failed, and now you were asked about ‘comparative PK’? I never came across such a term. The following is the guidance.... To use pharmacokinetics (PK) bridging only, you should establish bioequivalence between test drug the listed drug under both fasting and fed conditions. If the bioequivalence cannot be established due to different food effect or other reasons, you should demonstrate comparable PK and pharmacodynamics (PD) between Test and reference. To establish "comparable PK" between test and reference, the active drug exposure (AUC, Cmax and Ctrough) of test at the proposed dosing regimen should be comparable with the listed drug. Thanks |
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Helmut ★★★ Vienna, Austria, 2021-05-12 18:18 (1308 d 21:31 ago) @ PVRC Posting: # 22347 Views: 2,851 |
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Hi PVRC, can you give us the context? Which guidance are you referring to (a link would be nice)? Did you really fail to show BE? — 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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jag009 ★★★ NJ, 2021-05-20 03:31 (1301 d 12:18 ago) @ Helmut Posting: # 22359 Views: 2,695 |
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Hi Helmut, ❝ can you give us the context? Which guidance are you referring to (a link would be nice)? Did you really fail to show BE? Maybe he meant to use clinical endpt to demonstrate equivalence? J |
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PVRC ☆ India, 2021-05-20 09:41 (1301 d 06:08 ago) @ Helmut Posting: # 22361 Views: 2,692 |
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❝ can you give us the context? Which guidance are you referring to (a link would be nice)? Did you really fail to show BE? Hi Helmut, the description given is not from the guidance but from the responses from FDA to one of the questions in the pIND meeting. FDA recommended to demonstrate comparable PK in case bioequivalence is not established for different reasons in the fasted and fed state. Thanks with best regards |
Ing. Helmut Schütz