FY2016 Regulatory Science Report: Transdermal Drug Products
This section contains only new information from FY2016. For background scientific information and outcomes from previous years on this research topic, please refer to the FY15 Regulatory Science Research Report on Transdermal Drug Products.
Introduction
To ensure the quality and performance of generic transdermal delivery systems (TDS) products and their robust therapeutic equivalence to their corresponding reference listed drugs (RLDs), multiple initiatives are underway to support research in this area. One of these initiatives characterizes the potential difference in heat effects in brand-name vs. generic TDS products. TDS products that are bioequivalent to their corresponding RLDs under normal conditions may deliver drug(s) at a higher rate than the RLD when both are exposed to the same elevated heat conditions that can occur during the normal course of product wear, such as from heating blankets, hot showers, and saunas.
Research
Two grants supporting research in this area provide the comparative assessment of TDS heat effects in vitro, using an in vitro permeation test (IVPT) model with excised human skin mounted on static Franz diffusion cells or on flow-through diffusion cells, and in vivo blood level PK studies in human subjects. One goal of this research is to develop appropriate and relevant study conditions under which to evaluate TDS heat effects - whether studying these heat effects in vivo in human subjects or in vitro using excised human skin on diffusion cells. Another goal is to elucidate the factors that influence how heat affects the release of drug from the TDS or the permeation of drug through the skin. Such factors may include the thickness or thermal resistance of the TDS, the physicochemistry of the drug or the TDS formulation, or the directionality of heat gradients, which are different when the elevated heat is environmental (external) as opposed to arising from elevated core body temperature (internal). An additional goal of this research is to develop computational models that can simulate the effect of heat on drug delivery from a TDS under a variety of different conditions, based upon studies conducted under one or a few conditions. The ultimate goal of this research is to develop predictive in vitro methodologies to evaluate the effects of elevated heat on an unintentional increase (internal or external) in transdermal delivery of drug(s) from TDS.
ORS staff facilitating research in this area
- Sam Raney, PhD, Priyanka Gosh, PhD, Tannaz Ramezanli, PhD, Yi Zhang, PhD, Markham Luke, MD, PhD
Projects and Collaborators
- Tiered Testing Strategy for Assessing Thermal Effects on Transdermal Products
- Site PI: Professor Kevin Li
- Grant #: 1U01FD004942
- Heat Effect on Generic Transdermal Drug Delivery Systems
- Site PI: Professor Audra Stinchcomb
- Grant #: 1U01FD004955
Publications
- Strasinger C, Raney SG, Tran DC, Ghosh P, Newman B, Bashaw ED, Ghosh T, Shukla CG. (2016) Navigating sticky areas in transdermal product development. Journal of Controlled Release 233:1–9
- Hao J, Ghosh P, Li SK, Newman B, Kasting GB, Raney SG (2016) Heat Effects on Drug Delivery Across Human Skin. Expert Opinion on Drug Delivery; 13(5):755-768.
- Abdallaha IA, Hammell DC, Stinchcomb AL, Hassan HE. (2016) A fully validated LC–MS/MS method for simultaneous determination of nicotine and its metabolite cotinine in human serum and its application to a pharmacokinetic study after using nicotine transdermal delivery systems with standard heat application in adult smokers. Journal of Chromatography B, 1020:67–77.
- Shin S, Ghosh P, Raney SG, Hammell DC, Hassan HE, Stinchcomb AL. Effect of Heat on Nicotine and Fentanyl Transdermal Delivery Evaluated In Vitro Using Different Skin/Membranes. Poster Presentation at the American Association of Pharmaceutical Scientists Annual Meeting (November 13, 2016)
Oral Presentations
- Stinchcomb AL. Bioavailability and Bioequivalence of Products Applied to the Skin. Invited Oral Presentation at the Third Bioequivalence Summit: Ensure Regulatory Compliance When Demonstrating the Bioequivalence of New Dosage Forms, Delivery Methods and Biosimilars, Boston MA. (September 26, 2016)
- Stinchcomb AL. IVIVC in Transdermal Drug Delivery: Streamlining the Drug Approval Process. Invited Oral Presentation at Transdermal and Intradermal Drug Delivery Systems 2016: Advanced Design, Development and Delivery of Skin-Mediated Therapies and Vaccines. (September 13, 2016)
- Raney SG (2016) The Impact of GDUFA Regulatory Science. Invited Oral Presentation at the Center for Drug Evaluation and Research (CDER) Scientific Rounds (April 27, 2016).
- Stinchcomb AL. Topical Bioequivalence: Performance Evaluation In Vivo & In Vitro by Skin Stripping & IVPT. Invited Oral Presentation at the American Association of Pharmaceutical Scientists Annual Meeting Symposium, Bio-Equivalence Standards for Topicals (BEST): Evidence for Integrating Multiple Quality (Q3) and Performance Tests to Evaluate the Best Generic Products (October 28, 2015)
- Stinchcomb AL. Challenges in the Development of Bioequivalent Topically Applied Drug Products. Invited Oral Presentation at the Second Bioequivalence Summit: Innovative Approaches Toward Developing Bioequivalent Drugs While Comprehensively Maintaining Regulatory Compliance (October 5, 2015)
Poster Presentations
- Thomas S, Ghosh P, Raney SG, Hammell DC, Hassan HE, Stinchcomb AL. Effect of Controlled Heat Application on Topical Diclofenac Formulations Evaluated by In Vitro Permeation Tests (IVPT) using Porcine and Human Skin. Poster Presentation at the American Association of Pharmaceutical Scientists Annual Meeting (November 13, 2016)
- Shin S, Ghosh P, Raney SG, Hammell DC, Hassan HE, Stinchcomb AL (2016) Effect of Heat on Nicotine and Fentanyl Transdermal Delivery Evaluated In Vitro Using Different Skin/Membranes. Poster presentation at the American Association of Pharmaceutical Scientists Annual Meeting (November 13, 2016)
- Zhang Q, Murawsky MK, La Count T, Hao J, Raney SG, Ghosh P, Kasting G, Li S. Evaluation of Heat Effects on Transdermal Delivery Systems Using an In Vitro Permeation Test (IVPT) Strategy. Poster Presentation at the American Association of Pharmaceutical Scientists Annual Meeting (November 13, 2016)
- Shin S, Ghosh P, Raney SG, Hammell DC, Hassan HE, Stinchcomb AL (2016) Effect of Heat on Nicotine and Fentanyl Transdermal Delivery Evaluated In Vitro Using Different Skin/Membranes. Poster presentation at the Fifteenth International Conference on Perspectives in Percutaneous Penetration. La Grande Motte, France (March 30, 2016)
- Thomas S, Ghosh P, Newman, B, Raney SG, Hammell DC, Hassan HE, Stinchcomb AL. A Pharmacokinetic Study of the Effect of a Standardized Exposure to Heat on Nicotine Transdermal Delivery in Adult Smokers. Poster Presentation at the American Association of Pharmaceutical Scientists Annual Meeting (October 28, 2015)
- Shin SH, Raney SG, Ghosh P, Newman B, Hassan HE, Stinchcomb AL. In Vitro/In Vivo Correlation (IVIVC) of Bioavailability from Nicotine Transdermal Drug Delivery Systems Under the Influence of Heat. Poster Presentation at the American Association of Pharmaceutical Scientists Annual Meeting (October 28, 2015)
- La Count TD, Li SK, Kasting GB. Computational Model for Estimating the Effect of Heat on Dermal Clearance in Skin Transport. Poster Presentation at the American Association of Pharmaceutical Scientists Annual Meeting (October 28, 2015)
- Shin SH, Thomas S, Aballah I, Raney SG, Ghosh P, Newman B, Hammell D, Hassan HE, Stinchcomb AL. Evaluation of Bioavailability and In Vitro/In Vivo Correlation of Nicotine Transdermal Drug Delivery Systems Under the Influence of Heat. Poster presentation at the Barrier Function of Mammalian Skin Gordon Research Conference (August 18, 2015)
Outcomes