Generic drugs are an attractive alternative for patients relative to reference listed drugs because generic drugs have the same treatment effect but are generally available at considerably lower costs. However, only a limited number of generic alternatives are available for topically applied dermatological drug products. One of the main reasons for this limitation is the requirement to demonstrate bioequivalence (BE) of the generic and the reference listed drug which is usually achieved by expensive and time-consuming clinical endpoint studies. Hence, there is an urgent need for more cost- and time-efficient, accurate, sensitive and reproducible methods that measure drug concentrations in-vivo in the skin. The current project application ?BE-TWO? builds on the completed US FDA co-funded project ?dOFM4BE? (2013- 2015) in which dOFM has demonstrated its successful application to assess BE and non-BE of topically applied hydrophilic creams. The new proposed project ?BE-TWO? addresses the need for more effective methods to assess BE of topical drugs based on in-vivo dermal pharmacokinetics. ?BE-TWO? will develop a general clinical dOFM set-up and a BE test for lipophilic and protein bound substances and establish dOFM as a reliable and easy-to-use method to accurately, sensitively and reproducibly measure BE of any topical dermatological product. To achieve this objective BE-TWO will (1) identify and evaluate factors which influence dOFM data variability for a hydrophilic API based on existing data from project ?dOFM4BE?, (2) identify and evaluate additional factors that potentially influence dOFM data variability by conducting a clinical study for lipophilic and protein-bound APIs, and (3) develop strategies to eliminate or minimize influencing factors in order to develop a highly standardized, generally applicable BE test method for all types of APIs which will be tested in a proof-of-concept study.
Generic drugs are an attractive alternative for patients relative to reference listed drugs because generic drugs have the same treatment effect but are generally available at considerably lower costs. However, only a limited number of generic alternatives are available for topically applied dermatological drug products. One of the main reasons for this limitation is the requirement to demonstrate bioequivalence of the generic and the reference listed drug. This is a demanding task for topical drugs because no general FDA-approved method is available for topically applied drugs to test for bioequivalence in the skin. Thus, manufacturers must rely on clinical endpoint studies, which are not only expensive and time consuming, but can also be rather unreliable. There is an urgent need for accurate, sensitive and reproducible methods that measure drug concentrations in-vivo in the skin. Building on recently developed bioequivalence testing by dermal open flow microperfusion the new project BE-TWO aims to develop a general open flow microperfusion set-up to reliably test the bioequivalence of topical dermatological drug products in a minimized number of participants.
