Bioequivalence and Bioavailability Forum

Dear ABE,

❝ Kindly let me know whether it is mandatory to keep same study design as given in Bioequivalence Recommendations by USFDA.

See e.g. the black box in the 2003 guidance:

This guidance represents the Food and Drug Administration's (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

My emphases. See also page 5 of the same guidance:

FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

All of FDA’s guidances (even finalized product specific ones) have the header

Contains Nonbinding Recommendations

on every single page.

In other words, you can use a different approach but have to have good reasons in doing so. I would be especially very wary to deviate from product specific guidances. As the FDA states:

[…] we also recommend that sponsors and/or applicants consult the appropriate review staff.

Note also that guidances are nonbinding to the FDA as well. Even if a study was performed exactly according to a guidance the study may not be accepted since the FDA has changed their ‘current thinking’ in the meantime. BTW, Barbara Davit pointed out at a BA/BE conference (Ljubljana, 2010) that according to a verdict by the federal supreme court there is no difference between draft and final guidances.