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

The heterogenous group of advanced therapy medicinal products (ATMPs) are biologics with frequently limited viral safety profiles. As compared to well-established biologics such as monoclonal antibody products, the risk of virus contamination is significantly higher for some ATMPs. The standard approaches and tools used to mitigate the viral risk have limitations, leaving open the chances of missing virus contamination in an ATMP manufacturing process in both upstream and downstream. Next-generation sequencing (NGS) technology can overcome the residual risk by having the potential to detect any kind of virus contamination based on its inherent capability to detect any kind of nucleic acid in a sample. It perfectly combines the benefits and compensates for the downsides of the existing testing tools. It will replace a bunch of different established testing methods at improved turnaround times and, in the end, reduced overall costs. The combination of these characteristics is making NGS-based virus testing an in-demand and preferred approach to mitigating the virus contamination risk across all kinds of biologics mid- and long-term.

Bioinformatics Biologics Production Cell & Gene Therapy Regulatory Risk Analysis and Management Viral Reference Materials Viral Vectors

Cell therapy has emerged as a promising technology that involves implanting live cells to replace/repair and restore normal function of damaged tissue. Autologous chondrocyte implantation (ACI) has been proven effective for the regeneration of articular cartilage in defective cartilage tissue. The process starts with the collection of healthy tissue from an eligible patient, then isolation and expansion of desired cells in vitro under good manufacturing practice (GMP) conditions, qualification before release of the final cell product, and finally, implantation into the patient. The promise to deliver autologous cell therapies has its own challenges in robust and reproducible manufacturing. To commercialize a cell therapy, it is imperative that a robust and scalable manufacturing process is set up that is consistent, in terms of quality and quantity, in order to deliver the intended therapeutic effect.

We analysed the manufacturing parameters of over 100 cartilage samples that were used to deliver our proprietary, commercialized autologous cell therapy. The paper addresses the most cited challenges in the manufacturing of autologous cell therapies and describes a robust process of in vitro human chondrocyte cell culture. Also included are key factors in manufacturing for attaining a high-quantity and quality product for articular cartilage regeneration.

Cell & Gene Therapy Manufacturing

Fujifilm Diosynth Biotechnologies (FDB) is a global contract development and manufacturing organization (CDMO) with over 25 years of experience in process development and/or manufacturing of greater than 310 molecules at sites in: Billingham, England; Research Triangle Park, North Carolina; and College Station, Texas. At our College Station location, we specialize in the development and manufacture of virus-based vaccines (attenuated or recombinant viruses), oncolytic viral therapies (such as adenovirus, polio) and gene therapy vectors (such as adeno-associated virus [AAV])…

Cell & Gene Therapy Viral Vectors

A rapid increase in the number of gene therapy trials and products has led to a comparable increase in the need for industrial production of viral gene therapy vectors such as lentiviral, adeno-associated, and adenoviral vectors. Current production systems are limited with respect to scalability and robustness. With our CAPĀ® and CAP-Tā„¢ cell lines, we have developed a novel system for high-density suspension culture, efficient and reproducible transfection, and highly efficient production of viral vectors. By upstream process optimization, we have obtained a robust and high-density fed-batch culture system which can be scaled in any current bioreactor format. A design-of-experiments approach has been employed to optimize transient production of lentiviral vectors with significantly higher titers than can be obtained with adherent HEK293T cells…

Biologics Production Cell & Gene Therapy

Today, technology has reached a point where organisms (bacteria, plant and animal cells) can be genetically engineered to produce specific macromolecules and perform complex chemical reactions. Hence, they are called ā€œcellular factories.ā€ Cellular factories have applications in: biomedicine (e.g., implanted insulin secreting cells for the management of diabetes); biotechnology (recombinant protein and enzyme production for pharmaceutical and food industries); bioremediation (toxic waste and pollutant clean-up); green chemistry (production of chemicals with minimum toxic bi-product generation); alternative energy generation (electricity and hydrogen production by bacteria); biosensors (e.g., devices housing ā€œcanary cellsā€, which can signal the presence of pollutants, viral agents, or toxic chemicals); bioreactive devices (that can detect low concentrations of chemicals, etc.)…

Biologics Production Cell & Gene Therapy

The aim of personalized medicine is to provide the customized treatment likely to work best for each individual. A narrow interpretation of the definition attributes the appropriate treatment to be based on the patientā€™s molecular phenotype. A broader interpretation includes cell-based therapies that are derived from a patientā€™s own cells, or cells from a related or tissue-matched donor. Basic research findings contributing to the knowledge of the molecular and cellular basis of immune-mediated control of cancer and infectious diseases have created opportunities to develop new forms of cell-based vaccination for cancer and chronic infections like HIV. Cell therapy laboratories have developed from their roots in bone marrow transplantation and blood banking into what can now be described as cellular engineering laboratories where cells can be isolated, enriched, transduced, activated, expanded and otherwise manipulated in ways to change or enhance the function of in vivo-derived cells for eventual reinfusionā€¦

Cell & Gene Therapy

One of the major concerns facing relatively young biotechnology companies once a lead product has been identified is the issue of manufacturing. Usually this involves the upscaling of a lab-scale process while at the same time, complying with good manufacturing practice (GMP) to ensure a reproducibly-produced and consistent product. It also involves the establishment of specific and robust assays in process controls and release criteria. This issue has become more acute in the EU since 2004 due to the EU Clinical Trials Directive requiring GMP-certified production of investigational medical products even for phase I trials. Startup biotech companies are often limited in their finances and resources, as well as being bound by tight milestones. Quite often the expertise in upscaling and GMP-compliant production as well as the facilities and equipment required are not available in-houseā€¦

Cell & Gene Therapy Manufacturing

In recent years, cell therapy has been suggested as a promising approach for repair and regeneration of damaged tissues. VesCellā„¢, a blood-derived autologous cell therapy product consisting of ex vivo enriched angiogenic cell precursors (ACPs) was developed by TheraVitae for the treatment of severe heart diseases. A non-mobilized, blood-derived cell population consisting of low density cells, termed synergetic cell population (SCP), was isolated and cultured in the presence of serum-free medium (X-Vivo 15, Lonza, Walkersville, MD, USA) supplemented with growth factors and autologous serum to yield VesCell. Significant cell numbers (>50×106) exhibiting morphological, immunocytochemical, and functional characteristics of the angiogenic cell lineage were obtained from blood samples. The ACPs expressed the hematopoietic stem cell (HSC) markers CD34, CD133 and CD117, as well as specific angiogenic markers such as vascular endothelial growth factor receptor 2 (VEGFR2) (receptor 2 [R2] is also known as kinase domain region [KDR]), CD144, and CD31ā€¦

Cell & Gene Therapy Manufacturing Uncategorized

Recombinant DNA-transduced cellular products encounter the product development and regulatory issues of both gene therapy and cellular therapy products. The characterization of recombinant DNA-transduced cellular products remains highly challenging for both sponsors and regulatory agencies. The regulatory concerns and product testing for such cellular products are similar to those for all biologicals. These concerns include the demonstration of product safety, identity, purity, and potency; the control of the manufacturing process to ensure the consistency of product manufacturing under a proper quality control program; and the demonstration of reproducibility and consistency of product lots by means of defined product lot release testing criteriaā€¦

Cell & Gene Therapy Regulatory

Since the first gene therapy trials were conducted 25 years ago, there have been high expectations from the public, and much attention from investors, that previously incurable diseases would be cured by gene therapy. Still, despite numerous gene therapy clinical trials for many different indications, there are no approved gene therapy drugs in the United States. In 1999, one gene therapy patient died during clinical trials, the first ever. This highly publicized event led to heightened regulatory scrutiny over all such trials. Then in 2003 and 2005, three subjects developed leukemia as a direct consequence of gene therapy; one of them eventually passed away. The regulatory response stemming from these incidents led to greater regulatory oversight in gene therapy, as compared to other investigational drugs and biologics…

Cell & Gene Therapy Regulatory