Drugs

Report Highlights Research Priorities for Transdermal Generics

A new CDER report on developing generic drug transdermal delivery systems (TDS) outlines research efforts under the previous (2012 to 2017) generic drug user fee program and highlights future directions mandated by the current program. FDA has long recognized the special challenges associated with evaluating therapeutic equivalence for generic TDS products (e.g. skin patches). “For example, FDA was aware of specific issues related to determining statistical non-inferiority for TDS adhesion, irritation and sensitization in clinical studies,” the report says. FDA has also been concerned with the potential effects caused by high temperatures on TDS products, and differences between proposed generic TDS products compared with innovator products in composition or design could mean that the TDS products may respond differently to heat.

As for future directions, FDA says it needs complete certain research, such as “understanding the general applicability of the newly-developed TDS characterization tools to a wide variety of TDS products. Further research is also needed so that additional tools and techniques can be developed, which may include new methods to control advanced manufacturing processes for TDS products and transdermal gels, studies to better understand how different transdermal gel (pump) packaging and TDS designs and/or formulations may need to be controlled, and techniques to ensure the stable performance of a transdermal product throughout its shelf life.”

Ongoing research will also direct new projects. For example, the Critical Path Initiative is evaluating X-ray diffraction, differential scanning calorimetry, microscopy and near infrared hyperspectral imaging to characterize crystallization phenomena in rotigotine TDS. “The ongoing development of computational modeling approaches will likely facilitate more efficient product development and regulatory decision-making for transdermal products,” the report says.

“In silico models,” it continues, “could help to predict the influence of tapes or overlays on TDS drug delivery, the impact of varying degrees of TDS detachment on the resulting PK [pharmacokinetic] profile for a given product, the influence of differences in adhesion characteristics between products on BE [bioequivalence], or the extrapolation of single-dose PK data to simulated multi-dose PK profiles. Other ongoing research involving data mining is focused on statistical innovations to optimize the power and efficiency of in vivo studies. For example, FDA’s OGD and the Office of Translational Sciences, Office of Biostatistics are collaborating on research to evaluate potential enhancements to the designs and statistical evaluation of TDS irritation and sensitization studies, in a manner analogous to what was developed for TDS adhesion studies.”

Overall, the agency says the goal of generic drug science and research activities is to develop generally applicable BE approaches and supplemental regulatory standards for all types of transdermal products.

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

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