Maximum Daily Dose (MDD) of Cream Formulation

Confirmatory Testing & Analytical Challenges
1

Hello,
I would like to ask for your guidance regarding the following question.

The dosage and administration of Mujonal Cool Cream are described as once daily, apply an appropriate amount, without specification of a quantitative amount per application. The approved indications include superficial dermatophytosis, such as tinea pedis (athlete’s foot), tinea cruris (jock itch), and tinea corporis (ringworm).

For the purpose of providing a standardized, quantitative reference for topical application, the Finger-Tip Unit (FTU) concept is widely used in dermatology. The FTU was first introduced by C.C. Long and A.Y. Finlay and is defined as the amount of cream or ointment expressed from a standard tube nozzle (approximately 5 mm in diameter) along the distal phalanx of an adult index finger. This concept was formally described in the publication*“The finger‑tip unit — a new practical measure”*, published in Clinical and Experimental Dermatology in 1991.

I have some several questions regarding the application of the Finger‑Tip Unit (FTU) concept.

Given that one foot corresponds to approximately 2 FTUs, is it scientifically appropriate to define two feet as 4 FTUs and to adopt this value as a MDD for daily topical application?

Given that tinea cruris (jock itch) is included among the approved indications, should this indication also be taken into account when defining the MDD for exposure assessment?

Is it appropriate to incorporate the potential use on the groin area into the worst‑case FTU calculation, or can be reasonably defined based on a single indication (e.g., tinea pedis) without cumulative consideration of multiple indications?

If the assumed FTU value is increased, the resulting criteria may become excessively stringent. In such a case, how should this overly conservative assumption be appropriately managed or controlled?

20846S001LBL.PDF

According to the clinical data for Lamisil® cream, the product is administered once daily, with 0.5 g applied to a skin area of 12 × 8 cm for 7 days (with a treatment duration of 1 to 4 weeks depending on the type of infection). Furthermore, the resulting systemic exposure (AUC) is reported to be approximately 0.6% of that observed with oral terbinafine.

In light of these data, is it necessary to adopt highly MDDs for the exposure assessment, or can a less stringent approach be scientifically justified?

Thank you for your time and consideration.

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2

Dear KIM,

Based on my understanding, the Maximum Daily Dose (MDD) for topical products can be reasonably defined by estimating the maximum surface area associated with the approved indications and calculating the corresponding FTU‑based amount required for adequate coverage. Because bioavailability (BA) is not considered within the scope of ICH M7, systemic exposure is not used as a basis for defining the MDD.

Given that one foot corresponds to approximately 2 FTUs, I consider it scientifically appropriate to define the treatment of both feet as 4 FTUs and to adopt this value as the MDD for once-daily topical application. This is consistent with the FTU principle, in which the applied amount scales proportionally with the surface area requiring treatment.

When multiple indications are approved, we consider that the MDD should be determined using the indication associated with the maximum affected surface area. This provides a scientifically reasonable and transparent worst‑case assumption for exposure assessment, without introducing unnecessary over‑conservatism.

Yosuke

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