Jessica Knox, Study Director, Bioanalysis
For Skin Penetration Studies, Adaptability is Key
Bioanalytical support can reduce time to market
The U.S Food and Drug Administrations (FDA) ‘Bioanalytical Method Validation’ guidance for industry has helped to standardize the performance of bioanalytical method development and validation for in vivo studies. This is a positive step because it allows for a communal vocabulary.
However, at the time of writing, there are still no equivalent guidelines for the bioanalytical support for in vitro skin penetration studies, which assess the rate and extent of penetration of an active ingredient (AI) through the skin barrier and into the skin.
In 2016, and again in 2019, the FDA revised the ‘Draft Guidance on Acyclovir’. Acyclovir is an example AI in a topical cream and has been used to represent the current thinking of the FDA. This is the first document to give a comprehensive set of guidelines for bioequivalence (BE) studies and gives the choice of using in vivo or in vitro methodology. Where appropriate, this obviates the need for formal clinical trials in the development of topical generic therapies, which results in reduced development costs and an expedited route to market.
At the European Bioanalysis Forum Young Scientist Symposium last year I presented how we have been able to use these guidelines to increase bioanalytical support of in vitro studies, as well as outline the adaptations we have made to our processes in order to support bioequivalence studies. With this growth in bioanalytical capabilities, there is now more emphasis on ‘validating’ these assays, which again supports the discussion surrounding the need for standardized guidance.
For many years the bioanalysis team at Charles River has supported in vitro skin penetration studies, which range from pharmaceutical topical treatments to cosmetics. These studies are important to better understand the safety of topically applied materials. All samples collected during the lifetime of a study (including the excised skin and surrogate blood stream known as receptor fluid) are quantified using a developed LC-MS/MS assay to profile the activity of the AI.
Recently, we have also begun supporting in vitro BE skin penetration studies. BE studies are designed to demonstrate there is no significant difference in the rate or extent of an AI becoming available at the site of drug action between a reference formulation and the proposed alternative (or generic).
Within the bioanalysis group, we prove the suitability of our developed and validated assays to differentiate between the reference and generic formulations by assessing a third, deliberately different (in either concentration of AI or composition) formulation.
Bioanalytical support for in vitro studies can be fractured, with varied quality of data. Therefore it is important for our clients that they receive a consistent and high-quality service. We continue to build on years of experience and knowledge, working closely with the appropriate regulatory bodies, to offer the appropriate services for our clients and help streamline the process for them.
As this area continues to grow, we maintain regular contact with regulatory bodies to help mold the ‘gold standard’ and shape the future for bioanalytical support of in vitro skin penetration so that our clients can achieve their objectives and safely get their topical treatments to market.