Table of Contents
How do you calculate bioequivalence?
Bioequivalence is determined based on the relative bioavailability of the innovator medicine versus the generic medicine. It is measured by comparing the ratio of the pharmacokinetic variables for the innovator versus the generic medicine where equality is 1.
What are the methods of sample size determination?
There are two methods to determine sample size for variables that are polytomous or continuous. One method is to combine responses into two categories and then use a sample size based on proportion (Smith, 1983). The second method is to use the formula for the sample size for the mean.
What is T R ratio in bioequivalence study?
Bioequivalence (BE) trials aim to demonstrate that the 90% confidence interval of the T/R-ratio of the pharmacokinetic metrics between two formulations (test [T] and reference [R]) of a drug is fully included in the acceptance interval [0.80, 1.25].
What is CV in bioequivalence?
Abstract. The current study aimed to further contribute information on intrasubject coefficient of variation (CV) from 43 bioequivalence studies conducted by our center.
What is BA and BE studies?
BA/BE (Bioavailability & Bioequivalence) Studies. Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of generic version to its proprietary version of a drug or formulations of innovator drug in different clinical trial phases.
What is the difference between bioequivalence and bioavailability?
For a drug to be highly bioavailable it should be fast and completely absorbable. Bioequivalence is Just a comparison of the bioavailability of two identical products. For example, we compare two brands of paracetamol (Acetaminophen) for their bioavailability.
Why be criteria is 80% to 125%?
We also find that when Cmax OF T equals 0.8 and Cmax OF R is equal to 1.25, the corresponding ln(Ratio) equals to -0.223 and 0.223, respectively. This is the reason why the bioequivalence criteria are 80% – 125% based on the clinically significant ranges are +(-) 20% .
What is bioequivalence PDF?
bioequivalence confers the concept of therapeutic equivalence as: “A medicinal product is therapeutically equivalent with another product if it contains. the same active substance or therapeutic moiety and, clinically, shows the same efficacy. and safety as that product, whose efficacy and safety has been established.
How do you calculate intra CV?
Calculating Intra-Assay CV: The Average Coefficient of Variation between Duplicates. In this example cortisol concentrations are measured in duplicate for 40 samples. The % CV for each sample is calculated by finding the standard deviation of results 1 and 2, dividing that by the duplicate mean, and multiplying by 100.
What is intra-subject CV?
Intra-subject variability (CVintra), which determines the 90% confidence intervals and the number of subjects needed for assessment in bioequivalence studies, is generally investigated by using pilot study Results. However, conducting pilot studies greatly affects the speed and cost of drug development.
What sample size do we need for bioequivalence trials?
Sample size planning for bioequivalence trials needs assumptions on the relative bioavailability (BA) of tested products and the variability of the pharmacokinetic metrics. Some trial sponsors assume 1.00 as test–reference ratio, others use 5% or similar deviations from 1.00 to account for potential differences of the formulations.
How do you measure bioequivalence?
The designed approach was implemented using a simulation procedure considering some conventionally measured factors, such as geometric mean ratio and within-subject coefficient of variation, with various PK information important in determining bioequivalence. All simulation results were assessed according to the EMA and FDA guidelines.
How should we evaluate the bioequivalence of highly variable drugs?
Various approaches for evaluating the bioequivalence (BE) of highly variable drugs (CV ≥ 30%) have been debated for many years. More recently, the FDA conducted research to evaluate one such approach: scaled average BE.
What is the acceptance criteria for bioequivalence?
Bioequivalence acceptance was based on predefined criteria of 90% confidence interval (CI) of 80.00-125.00% for AUC parameters and reference-scaled-average bioequivalence of 71.73-139.42% for Cmax. The 90% CI for AUC0- t , AUC0-∞, and Cmax was 96.11-107.25%, 93.06-104.36%, and 94.23-127.01%, respectively.