> ## Content Index
> Fetch the complete content index at: https://www.fdaweb.com/llms.txt
> Use this file to discover other available public pages before exploring further.

# CDER Supports PBPK Modeling for Generic Bioequivalence
- URL: https://www.fdaweb.com/cder-supports-pbpk-modeling-for-generic-bioequivalence/
- Published: 2022-01-07T12:00:00.000Z
- Updated: 2026-09-14T17:27:51.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5150891

CDER is embracing industry’s use of physiologically based pharmacokinetic (PBPK) modeling as an alternative bioequivalence (BE) approach after approving a Perrigo Pharma ANDA for [generic diclofenac sodium topical gel](https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211253&ref=fdaweb.com) that does not include a comparative clinical endpoint BE study. In a just-published regulatory research [post](https://www.fda.gov/drugs/regulatory-science-action/how-modeling-was-used-support-fda-approval-topical-generic-drug-product?ref=fdaweb.com), FDA researchers say th*e* “benefit of applying PBPK models to support regulatory decision-making, especially for locally acting products, warrants further investment, collaboration and joint effort from the agency, industry, and academia.”

CDER researchers say the first approval relying on a PBPK model as a BE study alternative *“*provides a successful example of the utilization of novel quantitative modeling tools which were researched and published by FDA... The capability of the model to generate local and systemic diclofenac exposure predictions following the application of topical products that were sensitive to formulation differences was adequately validated.” They note that Perrigo used the recommended [pre-ANDA program](https://www.fda.gov/drugs/generic-drugs/pre-anda-program?ref=fdaweb.com) to obtain the agency’s feedback on the company’s alternative BE approach.

The researchers acknowledge that establishing BE for topical drug products by conducting comparative clinical endpoint studies can be costly, and the studies may not be sufficiently sensitive to detect certain formulation differences. “Quantitative methods and modeling (e.g., PBPK) can support alternative BE approaches with reduced or no human testing,” they say, but these mathematical models need to be sufficiently verified and validated for their intended purpose.