1. 1 Markham C. Luke, M.D., Ph.D. Dermatology Clinical Team Leader DDDDP, ODE V, CDER, FDA Combination Topical Products for the Treatment of Acne Vulgaris

2. 2 Fixed-combination Drugs “Two or more drugs may be combined in a single dosage form when each component makes a contribution to the claimed effects and the dosage of each component (amount, frequency, duration) is such that the combination is safe and effective for a significant patient population requiring such concurrent therapy as defined in the labeling for the drug.” - 21 CFR 300.50 (a)

3. 3 Acne Combination Drugs Combination topical products for the treatment of acne vulgaris require evidence for the contribution of each active component or components that are purported to provide for added efficacy.

4. 4 Fixed-combination Policy Applying the combination drug policy for 2 drugs, component substances A and B having the same endpoint, in a three or four arm clinical trial, success is demonstrated by: (A + B) > A, B > placebo

5. 5 Acne Combination Drugs Currently marketed combination topical drug products for acne have combined a topical antibiotic (erythromycin or clindamycin) [= A] with benzoyl peroxide [= B]. The safety and efficacy of other combinations for the treatment of acne are also being investigated.

6. 6 Acne Combination Drugs Studies to address the combination policy for acne drugs have shown that the most difficult superiority to demonstrate is the contribution of the antibiotic to the efficacy already achievable with benzoyl peroxide alone: (A + B) > B

7. 7 Conclusion Each component of a fixed combination drug for the treatment of acne must demonstrate a contribution to the claimed effects of the drug product. This may be difficult if the contribution of one of the actives (e.g., topical antibiotic) is minimal and hard to discern when combined with another active (e.g., benzoyl peroxide).