Bioequivalence and Bioavailability Forum

Hi Beholder,

❝ But why did FDA deside to use 1/10 or 100,000 rule? […] 100,000 is just round number and that's all?

We find nice numbers which are “easy to remember” everywhere.

• When the transition from analysis of untransformed [limits 80–120%] to log-transformed data was made, we had serious discussions about how the new limits should be defined. There were three parties (all considering a ∆ of 20% as not clinically relevant):
  1. L=1–∆, U=(1–∆)^–1 or 80–125%.
  2. U=1+∆, L=(1+∆)^–1 or 83⅓–120%.
  3. U–L 0.4 as the old one or ~81.98043–121.98033%.
  The 1^st party won because of the nice numbers.
  
• Critical dose drugs in Canada. ∆ 10% (like for the EMA). Lower limit 1–∆=90.0% (only one decimal place); upper limit not 111.11% but 112.0%.
  
• k in ABEL based on the switching CV_wR 30% not \(\log{(1.25)}/\sqrt{\log{(0.30^2+1)}} = 0.7601283\ldots \) but rounded to 0.76.

See also the BE GL Section 4.1.2

1. The test product should usually originate from a batch of at least 1/10 of production scale or 100,000 units, whichever is greater, unless otherwise justified.
   
2. The production of batches used should provide a high level of assurance that the product and process will be feasible on an industrial scale.
   In case of a production batch smaller than 100,000 units, a full production batch will be
   required.

(my emphasis)

prod. scale  full batch    10%    rule  biobatch
    50,000      yes        5,000    b     50,000
   100,000       no       10,000    a    100,000
 1,000,000       no      100,000    a    100,000
 5,000,000       no      500,000    a    500,000

Duno which justification you could give for a smaller biobatch under condition a).