PVRC
☆    

India,
2021-05-10 18:12
(41 d 14:23 ago)

Posting: # 22338
Views: 564
 

 Comparative PK [Study Per­for­mance]

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....
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2021-05-12 11:25
(39 d 21:11 ago)

@ PVRC
Posting: # 22345
Views: 449
 

 Comparative PK?

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, :blahblah:). 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 🖖
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
PVRC
☆    

India,
2021-05-12 15:48
(39 d 16:47 ago)

@ Helmut
Posting: # 22346
Views: 446
 

 Comparative PK?

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
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2021-05-12 16:18
(39 d 16:17 ago)

@ PVRC
Posting: # 22347
Views: 443
 

 Comparative PK?

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 🖖
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
jag009
★★★

NJ,
2021-05-20 01:31
(32 d 07:04 ago)

@ Helmut
Posting: # 22359
Views: 303
 

 Comparative PK?

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
PVRC
☆    

India,
2021-05-20 07:41
(32 d 00:55 ago)

@ Helmut
Posting: # 22361
Views: 295
 

 Comparative PK?

» 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
Activity
 Admin contact
21,530 posts in 4,499 threads, 1,524 registered users;
online 8 (0 registered, 8 guests [including 3 identified bots]).
Forum time: Monday 08:36 CEST (Europe/Vienna)

Young man, in mathematics you don’t understand things.
You just get used to them.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5