Kiki B. Hellman

Biomedical Applications of Tissue Engineering Technology: Regulatory Issues

Novel emerging technologies such as tissue engineering, which utilize the approaches of molecular and cell biology, biotechnology, as well as materials science and engineering, are being used in the development of a wide range of biomedical products developed by industries regulated by the U.S. Food and Drug Administration (FDA). The FDAs mission is to promote and protect the public health by ensuring the safety and effectiveness of pharmaceuticals and medical devices, including those manufactured by novel technology, as assessed by scientific principles and methods. Regulatory review is conducted on a product-by-product basis. To accomplish its mission over the wide range of products in its regulatory purview, the FDA has six centers, each staffed with the scientific and regulatory expertise to evaluate the products in the centers jurisdiction. Recent legislative and regulatory changes are designed to simplify and facilitate the administrative process for evaluating novel combination products emanating from such interdisciplinary technology as tissue engineering and to resolve questions of product regulatory jurisdiction. Under the new procedures, the FDA may designate a lead FDA center for product review based on the primary mode of action of the combination product, with additional center(s) designated to assist in the evaluation in a collaborative or consultative capacity. In addition, FDA centers have increased their cooperation and information sharing with regard to evolving interdisciplinary technology. The FDA InterCenter Tissue Engineering Initiative was established to develop information on intercenter efforts in the evaluation of tissue engineering applications and to identify areas for further consideration. The FDA InterCenter Tissue Engineering Working Group, comprised of staff from the Center for Biologies Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Center for Drug Evaluation and Research (CDER), and Center for Veterinary Medicine (CVM) has developed a Draft Report considering recent developments in tissue engineering and scientific and regulatory issues in the product application areas. The Working Group has identified generic safety and effectiveness issues for consideration by the research and development community in its development of products. The FDA centers are using multiple approaches at their disposal in the evaluation of tissue engineered products including research, data and information monitoring, regulatory guidance, training and education, and cooperation with public and private groups.

Chapter II.17 – Tissue Engineering: Product Applications and Regulatory Issues

Publisher Summary The Food and Drug Administration (FDA) recognizes that an important segment of the products that it regulates arises from new technological achievements and innovations. One example is products developed through tissue engineering (TE) technology, i.e., tissue engineered medical products. Tissue engineering is the application of the principles of life sciences and engineering to develop biological substitutes for the restoration, maintenance, modification, improvement, or replacement of tissue or organ function. In the broadest sense, tissue engineered medical products span a spectrum of products including transplanted human tissues or organs (i.e., autologous or allogeneic tissue); animal tissues or organs (e.g., transgenic animals or xenotransplants); processed, selected, or expanded mammalian cells (e.g., somatic and genetic cellular therapies) in combination with or without biomaterials; and totally synthetic materials of biomimetic design. Both the range of products and the rapid evolution in product design have generated a certain degree of ambiguity in the definition of tissue engineered medical products. There is no precise and globally accepted definition for tissue-engineered products (TEPs).

Commercialization of regenerative products: the academic/industry partnership.

The Identification of barriers to the successful commercialization of regenerative products is critical to their ultimate delivery to the clinic and marketplace as well as to the establishment of a viable, self-sustaining industry. The 2010 member survey conducted by the Industry Committee of TERMIS-North America (TERMIS-NA) identified the major barriers to academia and industry (start-ups, development stage, and established companies). The most common barriers identified were as follows: (1) funding; (2) technology transfer/intellectual property (IP); and (3) market focus. The data also suggested that enhanced communication among the different stakeholders of regenerative medicine is important for successful product development. Partnering between academia and industry is a key link in the biotechnology value creation chain. These synergies are perhaps even more important in the field of regenerative medicine to achieve efficient and appropriate translation of innovation from academia into industrial laboratories. However, there are several impediments to the development of tissue engineering and cell therapy products. The first of these is that the field is still emerging, despite several notable commercial or technical successes (e.g., Dermagraft or Apligraf as skin substitutes). Nevertheless, this cannot be compared with, for example, the level of deployment achieved by monoclonal antibody technology. This can be seen by using, as a proxy, the values of mergers and acquisitions or billion-dollar range licensing deals involving these biologics. The second major impediment is the still negligible interest that the pharmaceutical industry (‘‘big Pharma’’), as an asset class, has expressed to date for deploying cell therapeutics, with the notable exception of Pfizer, which has sustained their effort in the field since 2008 as highlighted by its 2009 strategic alliance with Athersys. Notably, mid-size Pharma has exhibited more willingness to address the remaining technology risks; this is exemplified by the strategic decisions made by Genzyme and Cephalon, which partnered with Osiris and Mesoblast, respectively, as early as 2009. Taken further, it would appear that identification of the appropriate synergies between academia and industry with relevant partnership strategies would not only accelerate product development but also deliver the ultimate goal of successful commercialization. To address this specific topic, the Academia/Industry partnership, TERMIS-EU (Europe), and TERMIS-AM (Americas) Industry Committees invited: