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The biological safety of biomaterials used for implantable medical devices is usually determined by a series of standard tests that assess the effects that extractable substances have on cells in vitro and in simple short term animal studies. To use these tests to determine the suitability of materials for tissue engineering templates is inappropriate. This short essay discusses the issues that are involved.

Computer-aided 3D printing approaches to the industrial production of customized 3D functional living constructs for restoration of tissue and organ function face significant regulatory challenges. Using the manufacture of a customized, 3D-bioprinted nasal implant as a well-informed but hypothetical exemplar, we examine how these products might be regulated. Existing EU and USA regulatory frameworks do not account for the differences between 3D printing and conventional manufacturing methods or the ability to create individual customized products using mechanized rather than craft approaches. Already subject to extensive regulatory control, issues related to control of the computer-aided design to manufacture process and the associated software system chain present additional scientific and regulatory challenges for manufacturers of these complex 3D-bioprinted advanced combination products.

Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950's for vaccine production, and these "old" cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair.

The current definition of biomaterials differs vastly from it of just a decade ago. According to advancing technologies, it encompasses unpredictable materials such as engineered human cells and tissue. These biomaterials also have to be approved to use in health care business by regulatory authority, which are defined as drug, medical device, or biologics in the regulation. This Leading Opinion Paper addresses the regulatory issues of engineered human cells and tissue products using allogeneic cells that should have a great possibility to develop therapeutics for life-threating diseases or orphan diseases. Six allogeneic human cells and tissue products derived from neonatal or infant fibroblasts and/or keratinocytes were approved as medical devices or biologics in the United States as well as a hematopoietic cell product. For five of the seven products, well-controlled comparative clinical trials were conducted as pre-approval evaluation followed by post-approval evaluation. Although these products avoid a sterilization process usually used for medical devices, no serious malfunction that would lead to class 1 recall was reported. This article would provide insight for development of the engineered human cells and tissue., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Gene-therapy medicinal products are currently applied to patients enrolled in authorized clinical trials to demonstrate safety and efficacy. Given a positive outcome, marketing authorization can subsequently be achieved via the centralized procedure coordinated by the European Medicines Agency. With Regulation (EC) No. 1394/2007 in force, advanced therapy medicinal products, including gene- and cell-therapy products, can be excepted from the obligation of obtaining a marketing authorization via the centralized procedure under specific conditions (so-called "hospital exemption"). This hospital exemption allows the application of gene-therapy medicinal products prepared on a non-routine basis for an individual patient and used under the exclusive professional responsibility of a medical practitioner. Here, we explain the requirements to be fulfilled in order to fall under this exemption, the implementation of this regulation into the German national legislation, and its impact on gene-therapy product development in the future.

The European Medicines Agency (EMA) and the Committee for Advanced Therapies (CAT) are responsible for reviewing applications for marketing authorization for Advanced Therapy Medicinal Products (ATMP), which include (stem) cell-based medicines, for the ATMP classification and certification procedure, and to provide scientific advice to developers of ATMPs. The CAT, an expert committee dedicated to ATMPs, was established by the Regulation (EC) No 1394/2007 on Advanced Therapies. The CAT came into operation in January 2009. ATMPs are defined in this Regulation as gene therapy and cell therapy medicinal products, and tissue-engineered products. The US FDA's Center for Biologics Evaluation and Research is responsible for ensuring the safety, purity, potency and effectiveness of many biologically derived products, including blood intended for transfusion, blood components and derivatives, vaccines and allergenic extracts, and cell, tissue and gene therapy products for the prevention, diagnosis and treatment of human diseases, conditions or injury. Human cells or tissue intended for implantation, transplantation, infusion or transfer into a human recipient are regulated as human cells, tissues, and cellular and tissue-based products (HCT/Ps).

Whenever new technology emerges it brings with it concerns and uncertainties about whether or how it will need to be regulated, particularly when it is applied to human healthcare. Drawing on the recent history in the European Union (EU) of the regulation of cell-based medicinal products, and in particular tissue-engineered products, this paper explores the myths that persist around their regulation and speculates on whether the existing regulatory landscape in the EU is flexible enough to incorporate nanotechnology and other new technologies into healthcare products. By untangling these myths a number of clear conclusions are revealed that, when considered in the context of risk-benefit, make it clear that what hinders the uptake of new technology is not regulatory process but basic science.

The Japanese government has recognized the challenges its rapidly aging population presents, especially in terms of healthcare provision, and is focusing on the potential of regenerative medicine to address them. The country has consequently embarked upon a national program to support development of this field. In 1999 Japan initiated a national research project in science and technology, known as the Millennium Project, whose areas of research include tissue engineering covering skin, cornea, bone, cartilage, blood vessels, nerves and bone marrow. In this context, at a time when regulations for tissue engineered products are being developed and revised in the USA and at the European level, it is interesting to investigate what type of framework Japanese regulators have designed to deal with these products in order to see what lessons might be learnt by UK, US and EU regulators. This paper reviews negative and positive aspects of the current regulatory situation that applies to tissue engineered products in Japan but will mostly focus on examples of good practice, such as the pragmatism that underpins the Japanese regulatory strategy, the international involvement of the country when it comes to developing regulatory standards and the promotion of a supportive public environment.

Cardiac muscle engineering aims at providing functional myocardium to repair diseased hearts and model cardiac development, physiology, and disease in vitro. Several enabling technologies have been established over the past 10 years to create functional myocardium. Although none of the presently employed technologies yields a perfect match of natural heart muscle, it can be anticipated that human heart muscle equivalents will become available after fine tuning of currently established tissue engineering concepts. This review provides an update on the state of cardiac muscle engineering and its utilization in cardiac regeneration. We discuss the application of stem cells including the allocation of autologous cell material, transgenic technologies that may improve tissue structure as well as in vivo engraftment, and vascularization concepts. We also touch on legal and economic aspects that have to be considered before engineered myocardium may eventually be applied in patients and discuss who may be a potential recipient.

Animal experimentation is an integrated part of tissue engineering research. This paper investigates what scientists conducting such experimentation should reasonably take into consideration from an ethical point of view. It is argued that scientists should use their moral imagination in making fundamental ethical choices, in reflecting on legal regulation, in taking public opinion seriously, and in balancing human benefit and animal harm as expected outcomes of the experiments.