Impact of genetically modified organism requirements on gene therapy development in the EU, Japan, and the US.

Advanced therapies are emerging as an important class of medicinal products; among these, gene therapies are advancing at an exceptional rate. However, one of the major challenges for gene therapies relates to the additional regulatory requirements for genetically modified organisms. In this paper, we provide an overview of the regulatory requirements for genetically modified organisms in the European Union, Japan, and the United States.

Global regulatory progress in delivering on the promise of gene therapies for unmet medical needs.

The rapid expansion of the gene therapy pipeline in recent years offers significant potential to treat diseases with great unmet medical need. However, the unique nature of these therapies poses challenges to regulating them within traditional frameworks, even when developing in a single country. Various factors exacerbate the issues in commercializing products across regions, including the lack of established regulatory frameworks for developing gene therapy products in many jurisdictions.

Global Manufacturing of CAR T Cell Therapy.

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.

MSC-based product characterization for clinical trials: an FDA perspective.

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.

Regulation of xenogeneic porcine pancreatic islets.

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.

Considerations for tissue-engineered and regenerative medicine product development prior to clinical trials in the United States.

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.

Update on regulatory issues in pancreatic islet transplantation.

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.

The effects of stress on memory cytotoxic T lymphocyte-mediated protection against herpes simplex virus infection at mucosal sites.

Psychological stress has been shown to affect many components of the innate and adaptive immune responses to a variety of pathogens including herpes simplex virus (HSV). Mucosal tissues are clinically relevant sites of infection with HSV as well as with many other common pathogens. However, there is a scarcity of experimental evidence that stress affects mucosal immunity.