Bioequivalence for Topical Products—An Update

Abstract

With the exception of topical glucocorticoids, demonstrating bioequivalence between generic and reference topical products entails conducting clinical end-point trials which are both lengthy and expensive. Considerable effort has been channeled towards development and validation of alternative approaches to demonstrate bioequivalence of topical and transdermal products. The critical opportunity pathways identified by the FDA for the industry for topical bioequivalence include the following surrogate methods: in vitro studies, dermatopharmacokinetic method, dermal microdialysis and near infrared spectroscopy. This review provides an update of recent advances in these methodologies.

Development of performance matrix for generic product equivalence of acyclovir topical creams

“…In order to 82 determine BE of acyclovir topical cream products for treating 83 herpes simplex labialis, the primary endpoint is the time to 84 complete healing of lesions. This is particularly challenging for in vitro permeation studies and near infrared (NIR) spectroscopy 101 have been explored to demonstrate the BE of topical dermatologi-102 cal products (Lionberger, 2008;Narkar, 2010;Yacobi et al, 2014). 103 Yet these surrogate methods are even more prone to failures in 104 Placebo cream was also prepared in the same way but without 186 drug and pH adjustment.…”

Assessment of Topical Bioequivalence Using Dermal Microdialysis and Tape Stripping Methods

“…The draft guidance describing the general procedures for conducting a topical BA/BE study was published by the US Food and Drug Administration (FDA) in 1998. However, it has been withdrawn because of a number of criticisms, such as interlaboratory variations and lack of correlation between drug amount in SC and clinical efficacy (3,20).…”

“…Possible methods for the determination of BE of multisource topical drug products include clinical trials, pharmacodynamics, tape stripping (TS), dermal microdialysis (DMD), and other techniques. Among these, TS and DMD methods are declared to be the promising ones (1)(2)(3). The TS method, which was also mentioned as the dermatopharmacokinetics (DPK) method, is attracting increasing attention as a method with which to assess the rate and extent of topical drug bioavailability (BA) in the rate-limiting barrier of skin, the stratum corneum (SC).…”

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“…When a topical formulation is applied onto the skin and perfusate is pumped through the implanted membrane system, drug molecules from the topical formulation present in the dermal ISF diffuse (driven by the concentration gradient) into the lumen of the membrane, resulting in the presence of drug in the perfusion medium collected as dialysate. The dialysate is sampled at various intervals of time and the drug concentration in the dialysate can be determined quantitatively [20].…”