Category: <span>Cell & Gene Therapy</span>

An astonishing range of viruses has provided building blocks for gene delivery systems, from the simple adeno-associated virus with a 5 kb genome to the complex poxviruses with 300 kb. This review focuses on non-replicating viral vectors that infect host cells just once, without producing infections virus. Viral vectors are generally characterized by several criteria, including their ability to integrate into the host genome, coding capacity, titer, toxicity, immunogenicity, host range, duration of gene expression, and transient or stable production systems. These are precisely the features that need to be carefully studied in the context of the application when deciding which vector to use…

Biologics Production Cell & Gene Therapy Viral Vectors

Cellular therapy is currently generating great interest in the treatment of a variety of diseases. In turn, this interest has stimulated the Center of Biologics Evaluation and Research of the Food and Drug Administration to examine its regulatory approach to the products used for these therapies. As a result, facilities preparing cell therapy products are now regarded as manufacturers, and are expected to comply with current Good Manufacturing Practices and/or the proposed current Good Tissue Practices. Compliance with these practices can be a culture shock to some academic centers whose background is firmly in research. The FDA has indicated that there is a sliding scale of compliance depending on the phase of the clinical study. The difficulty for centers is deciding where they fall on the compliance scale, as well as determining what changes must be made to come into compliance. This article reviews some of the factors that must be considered when making these decisions…

Cell & Gene Therapy Manufacturing Regulatory

As product development proceeds in the field of cellular therapies, adequate product characterization remains a challenge for both IND Sponsors and FDA/CBER. Cellular therapy products are not considered to be well-defined products, and therefore the control and characterization of each stage of the production process helps to ensure product safety and consistency. Product characterization of cellular products includes demonstration of safety, plus determination of identity, purity, potency, and product stability. Development of appropriate specifications for each of these parameters is necessary for lot release, and also provides an important database of knowledge for addressing regulatory issues, such as lot-to-lot consistency and potential issues with product comparability, should the manufacturing process, or other aspects of product development, change over time…

Cell & Gene Therapy Regulatory

We have developed a procedure for large-scale enrichment, growth and harvesting of T cells suitable for adoptive immunotherapy. In two recently completed clinical trials, we investigated the feasibility of immune reconstitution in patients with HIV infection, or with relapsed/refractory Non-Hodgkin’s Lymphoma (NHL) following infusions of autologous activated CD4+ T cells or CD4+/CD8+ T cells. Autologous T cells were activated via CD3/CD28 stimulation, ex vivo, and were then reinfused…

Cell & Gene Therapy

In orthopedic procedures, there is a need to form new bone to repair and fill defects arising from either trauma or degenerative disease. The current standard treatment utilizes an autograft, usually from the iliac crest, which results in a second surgical site, weakness in the harvest or donor harvest area, and additional patient morbidity. The goal of our research is to employ a local, ex vivo, gene therapy to obviate the need for autograft in spine fusion procedures. The LIM Mineralization Protein (LMP-1) is a novel intracellular protein capable of inducing bone formation in vitro and in vivo. In this article, I will outline a rapid protocol, whereby buffy coat cells, isolated from autologous peripheral blood, are transduced with an adenoviral vector encoding the LMP-1 gene. These transduced cells are then implanted on a collagen carrier to promote posterolateral arthodesis…

Cell & Gene Therapy

As you stand on the brink of finalizing your first Investigational New Drug (IND) application for a cellular therapy product, there is always the question looming in the back of your mind. “What did we forget?” Hopefully, the answer is “Nothing.” However, it is always good to undergo a review of the standard systems needed in order to transition from research to clinical manufacturing. This article describes an overview of the basic regulatory guidelines and quality systems necessary to begin clinical trials under the regulations of the Food and Drug Administration. However, this should only be considered a guideline, as it does not necessarily address the standards of other regulatory agencies. The investigational product, the clinical indication, and the manufacturing materials used in the investigational product can also change the regulatory requirements needed to proceed with the initiation of clinical trials…

Cell & Gene Therapy Manufacturing Regulatory