Bioequivalence and Bioavailability Forum

Hi there,

Can someone please let me know, if you have had experience with bioequivalence study with Adapalene 0.1% cream.

In UK, Adapalene is indicated for cutaneous treatment of mild to moderate acne vulgaris.

FDA guidance recommends bioequivalence study with clinical endpoints.
two primary endpoints of the study are
1) percent change from baseline to week 12 in the inflammatory (papules and pustules) lesion counts and
2) percent change from baseline to week 12 in the non-inflammatory (open and closed comedones) lesion counts.
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM191958.pdf)

Lehman et al developed a surrogate PD model (pharmacodynamic (PD) assay) with daily applications of products containing tretinoin or adapalene to the forearms of human subjects for up to 21 days. Percutaneous absorption was enhanced through the use of polyethylene film occlusion (5 h). Pharmacologic activity was assessed through the daily measurement of three cutaneous responses intimately linked to retinoid-induced changes in epidermal differentiation:
(1) erythema;
(2) exfoliation (scaling/peeling), and
(3) increased transepidermal water loss.
(http://www.ncbi.nlm.nih.gov/pubmed/?term=adapalene+bioequivalence)

My requirement is to submit to MHRA. As individual product specific guidance is not available on EMA site, I am not sure about the regulatory requirement. As Adapalene is a retinoid-like compound, instead of clinical endpoint study (as recommended by FDA) can we do a surrogate PD model study (Lehman et al) to show bioequivalence?

Thank you,
Kind regards,
CR