COMMENTARY: Animal Models and Their Contribution to the FDA Approval Process for Topical Agents and Devices

I am pleased to address the readership of Wounds on this occasion of the second issue dedicated to animal models and their roles in wound repair and infection. I would like to take the Reader through a recent set of published experiments that examined a new experimental bandage using both the preclinical and clinical wound healing and infection models of our laboratory. This device was approved by the Food and Drug Administration (FDA) for the over-the-counter consumer and was launched in January of this year. The name of the device is Band-Aid® Liquid Bandage, LAB. It is being marketed by Johnson & Johnson after having been developed by Closure Medical Inc. This device is an octyl-2-cyanoacrylate liquid that is applied with a foam-tipped applicator, which has an accelerator incorporated into it. When applied with this applicator, the liquid polymerizes forming a protective film. The liquid bandage provides almost instant hemostasis to partial-thickness wounds. Many companies approach our laboratory to gather data that is useful in supporting applications for the FDA, and we use the porcine models we have developed over the years for this purpose. Our group had several questions regarding this product’s use. The first questions we addressed were: 1) Does the octyl-2-cyanoacrylate act as an occlusive dressing and stimulate keratinocyte migration? and 2) Is the material toxic to wounds? To answer these questions, we preformed our standard wound healing protocol, which was first published in 1978.[1] We compared LAB to a hydrocolloid dressing and to no treatment and measured complete reepithelialization over time. The results of these studies are published in Dermatological Surgery by Stephen Davis, Assistant Professor in the Department of Dermatology and Cutaneous Surgery, and other members of our group at the University of Miami School of Medicine.[2] We found that LAB was not toxic to wounds and, in fact, acted as an occlusive dressing. An important point to note is these studies and others that are submitted to the FDA require that testing be completed on six to eight animals to serve as source of statistically adequate data for the submission. We then tackled two other questions that came to mind: 1) What effect does the material have on bacteria that may be present in the wound? and 2) Can the material serve as an effective barrier against exogenous bacterial pathogens? Again, we evaluated this material in one of our porcine models, which has become one of the standard models for documenting product performance and claims for FDA submission. In order to evaluate the effect on pathogens in wounds, we inoculated wounds with known amounts of one of two wound pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. The wounds were then either treated with the LAB, treated with the hydrocolloid dressing, or left untreated. Next, in order to examine the ability of the liquid bandage to keep exogenous bacteria out of wounds, partial-thickness wounds were created, and wounds were either treated with the liquid bandage, treated with the hydrocolloid dressing, or left untreated. The surface and perimeters of the film were then inoculated with a known amount of either a suspension of Pseudomonas aeruginosa, a motile wound pathogen, or Staphylococcus aureus. Using a method adapted from the food industry, we quantitated the number of organisms in wounds. The results showed that the growth of two pathogens was reduced underneath the liquid bandage when compared to the hydrocolloid dressing and untreated wounds. Results also showed the material could provide an effective barrier against exogenous pathogens, which might be in the environment and contaminate the surface of dressed wounds. In-vitro work by Upvan Naranga, PhD, and his colleagues from Closure Medical detailing the early developmental work on the liquid bandage and our in-vivo work is accepted and pending publication in the Journal of Cutaneous Medicine and Surgery.[3,4] The encouraging results from the preclinical in-vivo studies supported the application for a controlled human clinical trial to the FDA. Following these preclinical in-vivo studies, we proposed performing controlled human studies on shallow dermatome wounds in volunteers, which resemble shallow abrasions rather than induced dermatome wounds. However, the FDA recommended that the study be conducted in “naturally occurring or real-world wounds”(cuts and abrasions). Our group also acted as one of the clinical sites to compare a standard Band-Aid adhesive bandage to the Band-Aid Liquid Bandage in volunteers. We believed that the recruitment of the real-world wounds would be difficult, but we were pleasantly surprised to rapidly recruit volunteers, obtain informed consent, and complete our portion of the clinical trial. This work is published in Dermatologic Surgery by William H. Eaglstein.[5] The road to developing a new wound healing product, from performing the initial toxicology, to performing the in-vitro, in-vivo, and human clinical wound healing studies, is a long one. Studies should be designed to answer potential questions of product use and effectiveness. It is an exciting accomplishment to participate in all aspects of supplying data for a new device that ultimately contributes to its acceptance and approval. The close collaboration that our research laboratory has with the clinical studies group within our department makes it all possible.