Search

Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion. Additionally, the challenges of taking a chimeric antigen receptor T cell manufacturing process from a single institution to a large-scale multi-site manufacturing center must be addressed. We have anticipated such concerns in our experience with the CD19 chimeric antigen receptor T cell therapy CTL019. In this review, we discuss steps involved in the cell processing of the technology, including the use of an optimal vector for consistent cell processing, along with addressing the challenges of expanding chimeric antigen receptor T cell therapy to a global patient population.

The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical trials utilizing xenogeneic porcine pancreatic islets to treat T1D.

Tissue-engineered and regenerative medicine products are promising innovative therapies that can address unmet clinical needs. These products are often combinations of cells, scaffolds, and other factors and are complex in both structure and function. Their complexity introduces challenges for product developers to establish novel manufacturing and characterization techniques to ensure that these products are safe and effective prior to clinical trials in humans. Although there are only a few commercial products that are currently in the market, many more tissue-engineered and regenerative medicine products are under development. Therefore, it is the purpose of this article to help product developers in the early stages of product development by providing insight into the Food and Drug Administration (FDA) process and by highlighting some of the key scientific considerations that may be applicable to their products. We provide resources that are publically available from the FDA and others that are of potential interest. As the provided information is general in content, product developers should contact the FDA for feedback regarding their specific products. Also described are ways through which product developers can informally and formally interact with the FDA early in the development process to help in the efficient progression of products toward clinical trials.

The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical trials utilizing xenogeneic porcine pancreatic islets to treat T1D.

Over the past 12 years, the US Food and Drug Administration (FDA) has reviewed more than 40 investigational new drug applications for the use of allogeneic pancreatic islets to treat type 1 diabetes mellitus. Recent advances in islet cell isolation, transplantation, and immunosuppressive maintenance have led to multiple centers reporting promising results in the treatment of type 1 diabetes with allogeneic islet cells. The FDA held an advisory committee meeting on October 9-10, 2003, to explore the potential for licensing allogeneic islets as a therapy for severe type 1 diabetes. This article highlights the manufacturing challenges, discussed by the FDA advisory committee, that remain to be resolved before allogeneic islets can be approved for treatment of type 1 diabetes. This article also briefly addresses the challenges facing the clinical trial design of studies that could be used to support licensure.

The progress made over the last few decades in understanding the genetic and immunological aspects of cancer has led to the development of a large number and variety of immune-based approaches to combat the disease. Among the products developed, or under development, have been receptor-targeted monoclonal antibodies (e.g., trastuzumab, tositumomab), cytokines (e.g., interferon-α [IFN-α], interleukin-2), growth factors (e.g., granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF1, erythropoietin), and an amalgam of innovative products collectively referred to as tumor vaccines.

Proposals submitted to the FDA for MSC-based products are undergoing a rapid expansion that is characterized by increased variability in donor and tissue sources, manufacturing processes, proposed functional mechanisms, and characterization methods. Here we discuss the diversity in MSC-based clinical trial product proposals and highlight potential challenges for clinical translation.