A Brief History of RECELL^® and Its Current Indications

Abstract

A concise history of the development of the RECELL^® device and the seminal work of Dr. Fiona Wood will be provided, as well as the current indications and potential future prospects for the use of RECELL^® in the United States.

The beginnings of RECELL^® date to the late 1980s, when Dr. Fiona Wood began investigating and developing techniques to maximize skin utilization for grafting burns. Driven by a desire to do more with less, what would ultimately become RECELL^® started with the humble attempt to sterilely homogenize autograft scraps in the operating room and spray the resulting suspension on donor sites. This initial approach was unsuccessful but served as the impetus for additional studies by Dr. Wood and her research partner, Dr. Marie Stoner, to try and develop a spray-on skin graft.¹ As their work evolved at the Western Australia Skin Culture Laboratory in Perth during the 1990s, the established intellectual property (IP) was transferred to the McComb Foundation starting in 1999 and subsequently licensed to the Australian company Clinical Cell Culture (C3). The initial commercial product from this partnership was CellSpray^®—a laboratory-cultured, spray-on, epithelial autograft—that was approved for the Australian market in 2001 and the European market in 2004. CellSpray^® is considered by many to be the precursor to RECELL^®.² Recognizing that a point-of-care skin grafting technology/technique would be far superior to a laboratory-based one, Dr. Wood pursued research that pushed the CellSpray^® platform in this direction. What eventually emerged was the RECELL^® technology. C3 brought RECELL^® to the European market in 2005 and to the Australian and Canadian markets in 2006. Unfortunately, throughout this entire time, neither CellSpray^® nor RECELL^® were commercially available in the United States.

In 2005, C3 initiated the U.S. Food and Drug Administration (FDA) approval process for RECELL^® along the 510(k) pathway. Since no U.S. studies had ever been performed with RECELL^®, the FDA requested U.S. clinical trial data to support the 510(k) application. A protocol was agreed upon, and enrollment began in the United States in April 2007.

The years 2008 and 2009 proved to be pivotal in the development of RECELL^®. In mid-2008, C3 was acquired by another Australian company, VisioMed, via a reverse-merger. The newly formed company was Avita Medical. Avita continued to support the U.S. FDA approval process for RECELL^®, but the approach evolved. In September 2008, enrollment in the initial preliminary U.S. clinical trial, originally sponsored by C3, was discontinued. Following the successful participation in a U.S. Department of Defense (DoD) Armed Forces Institute of Regenerative Medicine (AFIRM) clinical trial solicitation in late 2008, Avita was awarded a DoD AFIRM contract starting in early 2009 to fund a new phase 3 clinical trial to support the U.S. FDA approval for RECELL^®.

The AFIRM-funded clinical trial enrolled patients from May 2010 to September 2014 and compared treatment with RECELL^® as a primary epidermal autograft (EAG) to standard-of-care, split-thickness autograft (STAG) in adult patients with deep partial-thickness thermal burns.³ In consultation with the U.S. FDA, an additional phase 3 trial was planned to better define any reduction in skin graft requirements when RECELL^® was used as an over-spray EAG on top of more widely meshed STAG vs. standard-of-care meshed STAG in adults and children with deep, mixed-depth, thermal burns. This study was funded in part by Biomedical Advanced Research and Development Authority (BARDA) and ran from January 2015 to February 2017.⁴ These two phase 3 RECELL^® studies in the United States served as the basis for Avita’s submission of RECELL^® to the FDA for approval along the Premarket Approval (PMA) pathway in September 2017.^3,4 Ultimately, RECELL^® was approved for the market by the U.S. FDA in September 2018.

Currently, RECELL^® is approved for the following in the United States:

1. direct application to acute partial-thickness thermal burn wounds in patients 18 years of age and older;

2. application in combination with meshed autografting for acute full-thickness thermal burn wounds in pediatric and adult patients.

The future prospects for RECELL are innumerable. In the burn space, the adoption of RECELL continues to accelerate and grow, allowing for enhanced grafting capabilities with reduced autograft skin requirements—one can really do more with less. However, RECELL is not a panacea for all burns. With full-thickness burns, RECELL has limitations in that it requires a widely meshed STAG over which it is sprayed. Direct, primary treatment with RECELL alone as an EAG on a full-thickness burn is associated with unacceptable scarring. Introduction to the dermatologic space is just beginning, with anticipated broad adoption for outpatient use in treating multiple skin disorders (eg, vitiligo, etc…). Although provided in a self-contained “kit,” the current version of the RECELL device requires primarily manual work. Following enzymatic digestion of the small (≤6 cm²) EAG in a heated well within the device, the dermo-epidermal junction is physically disrupted, and cells are mechanically disaggregated from the EAG via “scraping” by the provider. The disaggregated cells are collected by aspiration, filtered, and reconstituted as an autologous skin cell suspension (ASCS) for immediate use. A single, 6 cm² EAG produces sufficient ASCS to cover 480 cm². Automation presents promising possibilities for the RECELL device via partial or complete automatization of the preparation process. Future providers will likely be using a radically different and more advanced RECELL device than currently available. The future is bright.

Supplement sponsorship: This article appears as part of the supplement “Skin Regeneration and Wound Healing in Burn Patients: Are We There Yet?,” sponsored by Mallinckrodt Pharmaceuticals.

Conflict of interest statement. J.H.H. has equity interests in Abbott Labs, AbbVie, Change Healthcare, and Imbed Biosciences. J.H.H. is a consultant to Avita Medical and Stratatech/Mallinckrodt Pharmaceuticals.