Bioequivalence and Bioavailability Forum • SABE or Normal BE?

SABE or Normal BE? [RSABE / ABEL]

posted by luvblooms – India, 2013-02-20 06:26 (4451 d 07:03 ago) – Posting: # 10074
Views: 12,236

Hi John

❝ Where do you get page 3? I only see page 2. Is your link correct or I am still sleeping here in the east coast USA? The document I read is dated "Finalized Sep 2009, Revised Dec 2012"

Looks like you need a cup of strong black coffee.
I was mentioning about page 3 of warfarin sodium guideline.

❝ FDA wants you to compare the intrasubject variation between test and reference which full replicate will give. Reason is that the difference needs to be minimal since the product is a NTI.

Just a thought, What if the variability in the reference product is higher than test? ;-)

❝ If a parameter passes ABE, it should pass SABE correct? Okay it doesn't necessary work the other way around. But in this case, since the intrasubject variability is less than 30% (as per FDA's info on the guidance), a properly powered study with an acceptable test formulation should have no issue passing both correct?

I totally agree to what helmut said

❝ For any CVWR <21.42% the acceptance range will be narrower than 80–125%. In other words, the test might pass ABE but fail rSABE.

I tried using FARTSSIE 17 to do some random calculations

Assuming Desired Power  80%   

alpha                    5%

intra-subject CV (ISV)   20.0%

Expected mT/mR Ratio     95%-105

Lower Equivalence Limit  90.0%

Upper Equivalence Limit 111.1%

sw                        0.1980422

n                       168

n-2                     166

t(1-alpha,n-2)            1.654084714

tau2                     -7.249747184

tau1                      2.502165029

Probt(2)                  0.999999988

Probt(1)                  0.198471525

1-b                       0.801528462



Required Sample Size   168

For A full replicate study

Assuming Desired Power     80%

alpha                       5%

intra-subject CV (ISV)     20%

Expected mT/mR Ratio (%)   95%-105

Lower Equivalence Limit    90.00%

Upper Equivalence Limit   111.00%

k (= sb2 / sw2)             1

sWR                         0.1980422

n                         168

n-2                       166

t(1-alpha,n-2)              1.654084714

tau2                       -7.203445249

tau1                        2.502165029

Probt(2)                    0.999999984

Probt(1)                    0.198471525

1-b                         0.801528458

   

Required Sample Size   84

Also remember
a) higher blood loss
b) higher drop outs
c) prolonged study durations ( 3 wash out periods of 21 days)

—
~A happy Soul~

Complete thread:

SABE or Normal BE? luvblooms 2013-02-19 05:07 [RSABE / ABEL]
- FDA: rSABE for NTIDs Helmut 2013-02-19 11:05
- SABE or Normal BE? jag009 2013-02-19 15:23
  - Sample size? Helmut 2013-02-19 17:25
  - SABE or Normal BE?luvblooms 2013-02-20 05:26
    - SABE or Normal BE? jag009 2013-02-20 15:20
    - SABE or Normal BE? Helmut 2013-02-20 15:45
      - SABE or Normal BE? ElMaestro 2013-02-20 16:08
        
        SABE or Normal BE? jag009 2013-02-21 17:10
        
        FDA’s example data sets Helmut 2013-02-21 17:18
        
        FDA’s example data sets jag009 2013-02-21 20:14
        
        FDA’s example data sets Helmut 2013-02-21 22:42
        
        FDA’s example data sets jag009 2013-02-22 15:46
        
        FDA’s example data sets Helmut 2013-02-22 16:33