How do you establish bioequivalence?
Two medicinal products containing the same active substance are considered bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and their bioavailabilities (rate and extent) after administration in the same molar dose lie within acceptable predefined limits..
How do you evaluate bioequivalence?
In general, bioequivalence is evaluated by comparing the bioavailability of the test, and the reference products, in crossover clinical studies on healthy subjects.
The study may include the evaluation of bioavailability of products administered with, and without, food..
How to calculate 90% confidence interval in bioequivalence study?
To calculate 90% confidence interval, the Student t-quantile at significance level α/2 = 0.05 was used (t(0.05, 4) = 2.13).
The calculated confidence interval (90% C.I. = 96-108%) was also found to be within the acceptance limits of 85-115%..
What are the methods of bioequivalence studies?
Bioequivalence studies can be conducted in a non-replicated or replicated fashion.
The standard two-period, two-formulation, two-sequence crossover study uses a non-replicated design.
In terms of statistical analysis criteria, therefore, an average bioequivalence approach is generally sufficient..
What is the method of determination of bioequivalence?
In principle, evaluation of bioequivalence should be based upon measured concentrations of the parent compound.
The reason for this is that Cmax of a parent compound is usually more sensitive to detect differences between formulations in absorption rate than Cmax of a metabolite..
Which statistical method is used for the analysis of bioequivalence?
Classical 90% confidence limits and the 2 one-sided t-test approach are operationally identical and are the methods of choice for assessing bioequivalence (Cmax and AUC).
When tmax is an important parameter from the clinical point of view then the use of non-parametric confidence intervals is recommended..
- Bioequivalence studies are performed to demonstrate in vivo that two pharmaceutically equivalent products (in the US) or alternative pharmaceutical products (in the EU) are comparable in their rate and extent of absorption.
- In bioequivalence studies, the plasma concentration time curve is generally used to assess the rate and extent of absorption.
- The approach is referred to as average bioequivalence (ABE) where the 90% confidence interval for the ratio of the average geometric means (test/reference) for AUC and Cmax must fall between preset regulatory bioequivalence limits from 80% to 125%.
