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Cellular therapies have moved to the forefront based upon promising results from clinical trials using both chimeric antigen receptor T lymphocytes to treat leukemia and other cell types to restore structure and function to tissues that have been damaged by disease or physical injury. The pace at which these treatments have evolved has posed a regulatory challenge to agencies, such as the Food and Drug Administration (FDA). This chapter describes how a specific regulatory strategy was developed and how it has evolved in response to the demand for these new therapies.

Tissue engineered medical products (TEMPs) use state-of-the-art technologies and offer the patients with alternative clinical options for diseases that conventional treatments may fail or be incompetent. However promising, this technology is comparatively new with very limited hands-on experiences with both manufacturing and clinical therapy. Of great significance to products with such complexity and novelty is the establishment of a complete jurisdiction framework and a standardization database so that the safety of the technique in clinical treatment can be ensured. Although different regulatory routes are adopted in different countries, risks are generally considered to be derived from the cellular components within the product, the material scaffolds, and potentially from the final products. This article is to provide an insight of the regulatory considerations and the role of China Food and Drug Administration (CFDA) in the supervision of TEMPs.

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009.

The regulatory environment for cell- and tissue-based therapeutic (CTT) products is rapidly evolving and drug regulatory agencies are working toward establishing a risk-based system in their regulatory approach. In Singapore, CTT products such as cell therapy products, stem cell products, and tissue-engineered products in regenerative medicine are regulated as medicinal products. CTT products are defined as articles containing or consisting of autologous or allogeneic human or xenogeneic cells or tissues that are used for or administered to, or intended to be used for or administered to human beings for the diagnosis, treatment, or prevention of human diseases or conditions. Currently, we have applied a risk-based tiered approach whereby high-risk CTT products (substantially manipulated products, products intended for nonhomologous use or combined/used in conjunction with a drug, biologic, or device) are regulated under the Medicines Act. A new standalone regulation for CTT products is being proposed under the Health Products Act where we propose to regulate the entire spectrum (high and low risk) of CTT products.

Although the European Union merely followed the initiatives of the United States and Japan by introducing special regimes for orphan medicinal products, it has introduced a special status for a new category of biological medicinal products, advanced therapy medicinal products (ATMPs), adopting specific associated regulations. European Regulation (which constitutes the highest legal instrument in the hierarchy of European law texts) [EC] No. 1394/2007, published in 2007, uses this term to define somatic cell therapy medicinal products, tissue-engineered products, and gene therapy medicinal products, possibly combined with medical devices. The stated objective was two-fold: both to promote their industrialization and market access, while guaranteeing a high level of health protection for patients. Since publication of the regulation, few marketing authorizations have been granted in Europe, and these have not been accompanied by commercial success. However, certain recent studies show that this is a growing sector and that France remains the leading European nation in terms of clinical trials. This round table brought together a panel of representatives of French public and private protagonists from the advanced therapy sector. The discussions focused on the conditions to ensure the success of translational research and, more generally, the French advanced therapy sector. These enabled a number of obstacles to be identified, which once lifted, by means of recommendations, would facilitate the development and success of this sector., (© 2015 Société Française de Pharmacologie et de Thérapeutique.)

Today, sterility of parenteral drugs is practically guaranteed. Well-defined procedures in the pharmaceutical industry enable effective protection against contamination by bacteria and fungi. In contrast, problems regarding microbial safety of advanced therapy medicinal products (ATMPs), especially of cell therapeutics, are at best only partially solved. The latter should be understood as a challenge for manufacturers, regulators, and physicians. Many of the manufacturing principles mentioned above are not applicable in production of cell therapeutics. Sterility of source materials cannot be guaranteed and the hitherto known procedures for sterilization are, as a rule, not feasible. Thus, the sterility of the final product cannot be guaranteed. Considering the extremely short shelf life of many cell therapeutics, sometimes only a few hours, the results from established methods for sterility testing are often available too late. Furthermore, the sterility of a test sample does not indicate sterility of the whole product. In most cases, conventional methods for pyrogen testing are not applicable for ATMPs. This paper demonstrates relevant limitations regarding microbial safety and pyrogenicity. Possibilities to overcome these problems are discussed and some novel solutions are proposed.

For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

Tissue engineering advance in supplying the reparative and reconstructive medicine with promising tissue engineered medical products(TEMPs) and the new therapy alternative. The related supervision and administration of TEMPs is being developed and the standard research of TEMPs is also in progress. The Food and Drug Administration(FDA) of the United States has treated TEMPs as combined products and supervised them according to the level of risk to patients. Lately, FDA has determined that the Center for Devices and Radiological Health (CDRH) should take charge of examination and approval of TEMPs, with the cooperation of the Center for Biological Evaluations and Research(CBER). The regulatory controls have been established respectively in European Union and Japan. In China, TEMPs are identified as medical devices combined with cells. The Department of Medical Device of the State Food and Drug Administration (SFDA) is responsible for the examination and approval of TEMPs, and National Institute for the Control of Pharmaceutical & Biological Products(NICPBP) is responsible for evaluation tests. The standards of TEMPs are formulated mainly by the American Society of Testing Materials(ASTM) and International Standardization Organization(ISO).