Bioequivalence and Bioavailability Forum

Dear Ahmed!

❝ All the regulatory guidlines talks about conducting Bioequivalence study

❝ in single dose and at steady state conditions.

Not all of the guidelines! Generally single dose studies are more sensitive in detecting differences between formulations, especially for rate parameters.

❝ For which type of drugs conducting a Bioequivalence study at steady

❝ state conditions is necessary.

Regulatory requirements for steady state studies depend on the type of formulation (modified relase), not on the drug. Steady state studies are generally not needed for immediate release formulations (except for drugs with nonlinear PK and low solubility).

❝ For performing Bioequivalence study at steady state whether the sample

❝ size calculation is same as that of single dose study.

In the vast majority of cases variability in steady state is lower than after a single dose (I know of only one rare example where variability was not reduced^[1]). Therefore your single dose sample size in steady state should give you at least equal power. If you want to be sure, you may opt for a pilot study (for a reasonable size see this post and followings).

❝ If Bioequivalence study is performed at steady state whether it will meet

❝ the acceptance criteria with small no of subjects than a single dose

❝ study.

Most likely (see above), but at least in the European Union steady state studies are no more accepted as a proper mean for a reduction in sample sizes of highly variable drugs (as proposed by Blume et al.^[2]). See also this post on HVDs.

1. EJ Van Hoogdalem et al.
   Multiple dose bioequivalence study with josamycin propionate, a drug with highly variable kinetics, in healthy volunteers
   Int J Clin Pharmacol Ther 34/5, 202-207 (1996)
   
2. H Blume et al.
   Advantages of a steady-state crossover design in assessment of bioequivalence of highly variable drugs: propafenone
   Eur J Pharmaceut Sci 2, 385-393 (1994)