FDA-regulated research: cellular therapy considerations

Gene and Cell Therapy Funding Opportunities in Horizon 2020: An Overview for 2014–2015

Recent decades have seen advancements in the management and treatment of difficultto- treat diseases such as cancer. A special class of therapeutics called cell and gene therapy has been introduced in the past 10 years. Cell and gene therapy products have strengthened the treatment options for life-threatening diseases with unmet clinical needs and also provided the possibility of a potential cure for the disease in some of the patients. Cell and gene therapy products are gaining recognition, and the interest in clinical development of cell and gene therapy products is increasing. Moreover, as the class of cell and gene therapy products is relatively new, there is a limited regulatory experience in the development, and the developers of the cell and gene therapy products can often be puzzled with an array of questions on regulations. The current review intends to provide a basic understanding of regulatory guidelines from the FDA and EMA that are applicable to cell and gene therapy products. Essentials such as which office is responsible for the evaluation of applications, which regulatory class/pathway is appropriate for development, and what are the quality, nonclinical and clinical studies that are needed to support the application are discussed in the article. In addition, a summary of regulatory designations and the post-approval requirements, such as Risk Evaluation and Mitigation Strategies (REMS) and long-term follow- up, is included in the article. Developers (referred to as 'sponsors' in this article) of cell and gene therapies can use the respective guidance documents and other specific review articles cited in this review for detailed information on the topics.

Expanded Opportunities for Methods and Clinical Development

Introducing a New ASGCT Forum for Publication of Methodology and Clinical Development in Gene, Cell, and Oligonucleotide Therapies

Cell and Gene Therapy medicinal products need a tailored and integrated approach

Development of a Web Course on Gene Therapy by the International Consortium of Gene Therapy

Cancer is one of the world's most concerning health problems and poses many challenges in the range of approaches associated with the treatment of cancer. Current understanding of this disease brings to the fore a number of novel therapies that can be useful in the treatment of cancer. Among them, gene and cell therapies have emerged as novel and effective approaches. One of the most important challenges for cancer gene and cell therapies is correct monitoring of the modified genes and cells. In fact, visual tracking of therapeutic cells, immune cells, stem cells and genetic vectors that contain therapeutic genes and the various drugs is important in cancer therapy. Similarly, molecular imaging, such as nanosystems, fluorescence, bioluminescence, positron emission tomography, single photon-emission computed tomography and magnetic resonance imaging, have also been found to be powerful tools in monitoring cancer patients who have received therapeutic cell and gene therapies or drug therapies. In this review, we focus on these therapies and their molecular imaging techniques in treating and monitoring the progress of the therapies on various types of cancer.

Optogenetics: Controlling Cardiac Depolarization and Hyperpolarization Using Combined Cell and Gene Therapy and Light-Sensitive Proteins

Viral vector systems are crucial in delivering therapeutic genetic material for gene and cell therapy in clinical settings. With new progress in viral vector-based gene therapies, healthcare professionals and pharmacists must stay informed and apply appropriate biosafety precautions when handling these products. Comprehensive guidelines covering biosafety measures for every viral vector-based gene therapy, including storage, preparation, administration, and disposal, remain scarce. As viral vector-based gene therapy advances rapidly, it is critical to equip healthcare professionals with the expertise to safely manage these agents in a clinical setting. As gene therapies become more integrated into mainstream medicine, with 43 cell and gene therapy products approved as of 2025, pharmacists, nurses, and caregivers face new safety challenges when handling these therapies. While guidelines such as United States Pharmacopeia (USP) 797 and USP 800 provide a foundation for handling viral vector-based gene therapies, no single resource consolidates all biosafety considerations for healthcare professionals. This review provides an overview of the viral vector-based gene therapy landscape. It compiles best practices from various sources to establish a potential standardized approach to guide safe handling procedures for viral vector systems in a healthcare setting. By adopting the biosafety strategies outlined in this article, healthcare staff and pharmacists can safely manage viral vectors while developing standard operating procedures tailored to their specific clinical environments. Implementing these measures will support the continued advancement of gene therapy while ensuring the safety of healthcare providers, patients, and the environment.

After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.

Background aimsAlthough biologiocal ancillay materials (AMs) have specific risk associated with their derivations, it plays key role to manufature cell and gene therapy (CGT) products. It is important to understand the regulation relevant to AMs for developers. MethodsThe authors investigated the guidelines and pharmacopeia (hereinafter referred to as “guidelines”) for biological AMs used for the manufacture of CGT products in Asia (China, India, Japan, Korea and Taiwan). In addition, the authors benchmarked the relevant guidelines in the United States (US) and European Union (EU). Results and discussionsThe guidelines could be classified into two types based on whether specific AMs are scoped: (i) general guidelines for risk assessment of AMs and (ii) guidelines for specific AMs. The authors compared the risk categories for each type of AM provided in the general guidelines between the US and China and the specific requirements for bovine serum and trypsin in the guidelines of China, Japan, Taiwan, US and EU. The authors further compiled in-depth descriptions of the respective regulations in China, India, Japan, Korea and Taiwan. There is limited availability of some guidelines for specific AMs. Moreover, there are no common requirements established across the surveyed countries and regions. Therefore, the authors suggest a risk assessment approach for AMs with consideration of their biological origin and traceability, production steps applied and ability to control or remove AMs from the final medicinal product over the CGT manufacturing process.

Knowing thyself: an audit of cell therapy manufacturing in Australia and New Zealand

The FDA's Regulatory Framework for Chimeric Antigen Receptor-TCell Therapies.

Delivering externally manufactured cell and gene therapy products to patients: perspectives from the academic center experience

We read with great interest the meta-analysis by Mudgal et al. (2024) regarding the effectiveness and safety assessment of stem cell therapy for diabetic foot ulcers. Indeed, The management of chronic wounds requires innovative approaches to avoid unsuccessful outcomes, and stromal cell therapies have emerged as a potential solution for soft tissue repair. A critical aspect of this therapeutic strategy is the role of mast cells in stimulating delayed inflammation through their interactions with various cells as well as the extracellular matrix. Mast cells are critical in orchestrating the inflammatory response and their activation can influence macrophage behavior and secondary healing efficacy. The use of mesenchymal stromal cells in regenerative medicine for diabetic foot ulcers treatment is often limited by their time-limited anti-inflammatory responses. However, these time-limited effects could not achieve the prolonged effects and impact of cell therapy efficacy and the potential enhancement of cell function by biologically active factors such as growth factors or gene therapeutics for prolonged release. The integration of cell and prolonged release gene therapeutics is a promising approach that goes beyond regenerative medicine by preventing secondary inflammatory complications. While mesenchymal stromal cells have shown promising results in experimental and clinical studies, there are limitations to their efficacy in regenerative medicine for diabetic foot ulcers. These limitations include the heterogeneity of cell populations used in the studies, the difficulty in determining the contribution of cells when used in combination with materials, the lack of data on optimal cell numbers for tissue repair, the effect of culture conditions on cell therapy efficacy, and the potential enhancement of cell efficacy by the use of additional biologics such as growth factors or gene therapeutics. The combination of cell and gene therapy is seen as a promising approach that goes beyond regenerative medicine into the field of molecular surgery of chronic wounds.