“Classic dermal formulations cannot be easily assessed via usual bioequivalence clinical assays given that such topical products are not absorbed all the way to systemic bloodstream” he begins. “In fact, the EMA has been developing a draft guideline since 2018 in order to overcome unmet regulatory needs by means of transcutaneous diffusion devices called Franz cells.”
Dr. Celma goes on to explain this state-of-the-art assay: “We at Kymos have been developing our percutaneous absorption services according to OECD, FDA and EMA guidelines, and currently have not one but three of these fascinating instruments. Franz cells allow us to determine both drug permeation and drug release. We can perform absorption studies through skin, nails, mucosa or cornea, which combined with Kymos’ extensive analytical experience, allow us not only to quantify retained drug in the skin but also determine its distribution within each layer by stripping or thermal separation.”
In addition to these guidelines, both the EMA and the FDA began granting biowaivers for topical drug products which standardized in vitro Franz cell assays as an acceptable alternative to clinical trials. “Quite interestingly for topical generic manufacturers” Dr. Celma continues, “biowaivers for topical drug products establish that those companies are exempted from specific in vivo bioequivalence data if they can produce relevant in vitro data, as it is the case with Franz cells. Instead of rushing into an expensive and time-consuming clinical study, they now have the alternative to perform an in vitro percutaneous absorption study at Kymos.”
In the past years Kymos has performed several trailblazing in vitro permeation tests (IVPT), one of them with Kymos’ long-standing German client HELM AG. Between 2017 and 2019 Kymos identified the permeation/penetration profiles in human skin for HELM’s product in preparation for a clinical study. Dr. Marius Strunk, Senior Pharmaceutical Development Manager at HELM AG, comments on the study: “Back in 2017 there weren’t many analytical CROs able to carry out Franz cell assays and Kymos’ pioneering work was pivotal for the registration of our product: With the help of all the percutaneous absorption information they generated, our clinical phase III study went very smoothly, and we were able to demonstrate that topical treatment with our generic product is equivalent to the originator product. Soon the market will have another alternative for the treatment of chronic stable, mild to moderate plaque-type psoriasis” Dr. Strunk concludes.
Dr. Celma cannot help but sharing Dr. Strunk’s satisfaction: “Quite so, our data helped HELM design their clinical study more accurately, thus saving time and valuable resources” he begins. “It is always rewarding when our customers can take decisive steps in their product development process on the basis of our results. And we can always continue supporting them once development leads up to product manufacturing with quality control solutions based on the same EMA draft guidelines: Our in vitro release tests (IVRT), using artificial membranes, are a powerful tool to assist in the development and validation of release rates methods, characterization and optimization of topical formulations” Dr. Celma claims.
When asked about the future of this innovative service, Kymos’ Scientific Director is quite clear: “We began offering percutaneous absorption assays in 2017, when demand was still limited. Since then, our team has accumulated extensive know-how about vertical diffusion cells techniques and regulatory requirements, not to mention our new Franz cells Phoenix RDS automatic instruments. Now the EMA guidelines are close to completion and demand for these services is skyrocketing: The very moment we have been preparing for the last four years. Whether our clients require GLP-certified in vitro permeation or release tests under GMP, I honestly could not think of a better partner than Kymos to accompany them throughout the entire lifecycle of their topical drug product.”
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