Bioequivalence and Bioavailability Forum

Hi Joy,

❝ how to justify acceptable deviation of blood sampling time in BE studies ?

I’m not sure what you mean by justification here. There are many possible reasons which could justify a deviation: Technical problems (blocked venflow, difficulties in repeated venipuncure), logistics (subject arrives late for ambulatory blood draw), whatsoever.
Or do you mean the “magic” time allowance window (TAW)? Most CROs state in the protocol & CRF that sampling within the TAW must not be commented in the CRF. TAWs depend on the sampling schedule (increasingly wide). Example according to Papst* with an “irrelevant” deviation of 5% below:

scheduled ∆1    ∆2     TAW
  (h)     (h)   (h)    (min)
 pd                    –30
         0.25
 0.25            0.25   +1
         0.25
 0.5             0.25   +1
         0.25
 0.75            0.25   +1
         0.25
 1               0.25   +1
         0.25
 1.25            0.25   +1
         0.25
 1.5             0.25   +1
         0.25
 1.75            0.25   +1
         0.25
 2               0.25   +1
         0.25
 2.25            0.25   +1
         0.25
 2.5             0.25   +1
         0.5
 3               0.5    +2
         0.5
 3.5             0.5    +2
         0.5
 4               0.5    +2
         1
 5               1      +3
         1
 6               1      +3
         2
 8               2      +6
         2
10               2      +6
         2
12               2      +6
         4
16               4     +12
         8
24                     +12

∆1 is the difference between sampling time points. ∆2 is the smallest of two neighbouring ∆1s.
However, rarely I see only positive TAWs in CRFs. Most CROs state ±sumfink. I don’t get it & concur with Papst, who wrote:

Any sampling occuring too early is a deviation that should be reported even if pharmacokinetically irrelevant, since there are only a few plausible reasons why an activity should have been performed earlier than planned.

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• Papst G. Deviations in sampling times. In: Cawello W. (ed) Parameters for Compartment-free Pharmacokinetics. Aachen: Shaker Verlag; 2003. p. 78–79.