1. Updated Cross-Reference to the "Controlled Correspondence" Guidance
A supporting footnote referencing the guidance for industry *Controlled Correspondence Related to Generic Drug Development* has been updated:
- Draft cited the December 2020 version.
- Final cites the March 2024 version.
Action for industry: If relying on this footnote to locate FDA's controlled correspondence guidance, use the March 2024 version referenced in the final guidance, not the older one cited in the draft.
2. FDA Web Page Reference for Study Data Standards Updated
The footnote pointing readers to FDA's "Study Data for Submission to CDER" web page now points to a different (presumably updated/reorganized) URL in the final guidance than the one cited in the draft. Applicants preparing SAS XPT transport data sets and define files for adhesion study submissions should navigate to FDA's current study data standards page (linked in the final guidance) rather than relying on the older draft URL, which may be outdated or redirected.
3. Terminology Standardized to "PSGs"
The final guidance consistently uses the defined abbreviation PSGs (product-specific guidances) in places where the draft spelled out "product-specific guidance(s)" in full — for example, in the footnote describing where generic drug product-specific guidances are located, and in the discussion of BE criteria for PK analysis in Section IV. This is a stylistic/consistency change with no effect on substance.
4. No Identified Changes to the Core Scientific and Statistical Recommendations
Based on the visible text, the following substantive elements of the guidance appear unchanged between the draft and the final version:
- Recommended study designs (two-treatment, two-period crossover; or justified matched-pairs design)
- The five-point adhesion scale and its use for the noninferiority (NI) comparison of T vs. R
- Assessment frequency requirements tied to TDS wear duration (e.g., daily for 7-day wear, every 12 hours for 72-hour wear, etc.)
- The method for imputing/carrying forward the highest adhesion score over time
- The mean adhesion score formula and the weighted mean adhesion score formula for unequally spaced time points
- The prespecified noninferiority margin (δ = 0.15) and associated hypothesis testing framework
- Recommendations on per-protocol (PP) population definition, sample size/power (≥0.80), and handling of dropout/noncompliance
- Requirements for combined adhesion + bioequivalence (PK) studies
- Data submission format requirements (SAS XPT transport files, define file, raw and imputed data sets)
Action for industry: Sponsors who already designed adhesion studies in line with the April 2023 draft recommendations should not need to change their fundamental study design, adhesion scale, or statistical analysis plan based on this finalization — the core methodology carries forward.
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