Bioequivalence and Bioavailability Forum

Dear Kshitij!

❝ In different references we come across, various researchers have used the terms "comparative bioavailability" and "bioequivalence" for the similar studies.

Yes, some people like the sloppy use of terms. Sometimes you find “Comparative BA” in the title, “BE” in the abstract, and both terms in the article.

❝ However, as far as i understand, these imply to different kind of studies. the former (C BA) referring to all the studies involving comparison of bioavailability, while latter one (BE) refer to only those where a test product is being compared with the innovator's formulation (having same molar dose) only.

Exactly!

❝ This implies that, if we are comparing two generic products, the study should be termed as comparative bioavailability, not bioequivalence study. How about it?

Yes, that’s the correct term.

❝ Can we say that all BE studies are comparative BA studies,…

Yes, BE is a subset of comparative BA. You already gave the correct definition of BE above.

❝ …but all comparative BA studies are not BE?

Not quite.
Even if you have used the same molar dose, the innovator’s product as reference, etc., and all PK metrics found in the study were within commonly applied acceptance ranges – if your study was not planned to demonstrate BE (i.e., going for an abbreviated submission) it’s not a BE study.
Comparative BA studies report confidence intervals in a descriptive manner only; they are not confirmatory (as BE studies are).

So for bioequivalence we have three points to be fulfilled:

• Comparative BA,
  
• Designed to demonstrate BE,
  
• Reference = Innovator’s product.

❝ …can we use the two terminology interchangeably?

No.

❝ Please quote some references (preferably from regulatory bodies), if possible.

One “classical paper“* starts its summary with the sentence:

The role of comparative bioavailability trials in testing for the bioequivalence of different formulations of a drug is discussed and the statistical aspects of the design and analysis of such trials are reviewed.

The European Note for Guidance on BA/BE states at 3. Design and Conduct of Studies, 2^nd paragraph:

A bioequivalence study is basically a comparative bioavailability study designed to establish equivalence between test and reference products.

Similar wordings are given in other regulations.

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• Westlake WJ. Statistical Aspects of Comparative Bioavailability Trials. Biometrics. 1979;35(1):273–80. doi:10.2307/2529949.