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# Guidance on Skin Irritation Studies for Transdermal/Topical ANDAs
- URL: https://www.fdaweb.com/guidance-on-skin-irritation-studies-for-transdermal-topical-andas/
- Published: 2026-07-31T12:00:00.000Z
- Updated: 2026-09-14T13:44:13.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5161559

FDA has issued a revised draft guidance updating its recommendations for how generic drug developers should evaluate the skin irritation and sensitization potential of transdermal and topical delivery systems submitted in ANDAs.

The [guidance](https://www.fda.gov/media/167073/download?ref=fdaweb.com) provides recommendations for designing and conducting in vivo studies comparing proposed generic transdermal or topical delivery systems with their reference listed drugs. FDA said the latest revision clarifies study design recommendations for evaluating skin irritation and, where appropriate, sensitization, while also specifying circumstances in which a separate sensitization study may not be necessary.

FDA said transdermal and topical delivery systems can cause skin irritation or allergic sensitization because of their formulation, adhesive materials, or prolonged contact with the skin. Such reactions can reduce patient compliance, affect drug absorption, and alter product performance, making comparative safety assessments an important component of generic drug development.

Under the draft, applicants generally should conduct an in vivo irritation study for proposed generic products. A combined irritation and sensitization study is recommended when the generic contains an inactive ingredient not present in the reference product that is known to cause sensitization or is used at levels not previously approved in a similar product. FDA noted that sensitization studies are generally unnecessary when the active ingredient itself is a known skin sensitizer or when the formulation is the same as the reference product.

The guidance also expands recommendations for study conduct, including randomization, blinded evaluation of skin reactions, handling detached patches, subject eligibility criteria, and standardized scoring of dermal responses. FDA continues to recommend using the mean irritation score as the primary endpoint and evaluating whether the generic product is statistically noninferior to the reference product regarding skin irritation.

In addition to irritation scores, FDA said sponsors should analyze clinically meaningful outcomes such as severe skin reactions, discontinuations due to irritation, and application-site adverse events. The agency also provides recommendations for studies involving vehicle control patches, partial-cut transdermal systems, and the format for submitting study data in ANDAs.