Data Analysis and Labeling

The following exposure measures and PK parameters should be obtained from the resulting concentration-time curves for the test and reference products:

■ Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-f)

■ Lag-time (tlag) for modified release products, if present

■ Terminal elimination half-life

■ Other relevant PK parameters

Individual subject measurements, as well as summary statistics (e.g., group averages, standard deviations, coefficients of variation) should be reported. An equivalence approach is recommended analyzing data using an average criterion. Log-transformation of exposure measurements (AUC and Cmax) prior to analysis is recommended. The 90% CI for the ratio of population geometric means between test and reference products should be provided for AUC0-inf, AUC0-f, and Cmax. For ANDA fed BE studies, the RLD administered under fed condition serves as the reference treatment.

For an ANDA, BE of a test product to the RLD product under fed conditions is concluded when the 90% CI for the ratio of population geometric means between test and RLD product, based on log-transformed data, is contained in the BE limits of 80% to 125% for AUC and Cmax, respectively. Although no criterion applies to Tmax, the Tmax values for the test and reference products are expected to be comparable based on clinical relevance. The conclusion of BE under fed conditions indicates that with regard to food, the language in the package insert of the test product can be the same as the reference product.

Other Considerations Sprinkles

In ANDAs, BE of the test to the RLD is demonstrated in a single dose crossover study. Both treatments should be sprinkled on one of the soft foods mentioned in the labeling, usually applesauce. The BE data should be analyzed using average BE and the 90% CI criteria should be used to declare BE. If there are questions about other foods, the design, or the analysis of such BE studies, the sponsors and/or applicants should contact the Office of Generic Drugs.

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