Tag: <span>safety</span>

Cell substrates are used in various stages of viral vaccine manufacturing, as in the isolation, selection, and propagation of the virus seed or virus vector stock, as well as for the amplification of the virus to produce the final vaccine product. The various stages of cell substrate use, including cell banking, are shown in a generic manufacturing scheme in Figure 1. Traditionally, viral vaccines have been produced in animal tissues, primary cell cultures, and cell lines that either have a finite life span, such as normal diploid cells, or a theoretically infinite life span, as achieved with continuous or immortalized neoplastic cells. The cell substrates used in viral vaccines currently licensed in the US are listed in Table 1…

Manufacturing Viral Vectors

Contamination by adventitious agents (bacteria, fungi, mycoplasma, and viruses) represents potential safety risks for biologics produced in mammalian cells. Bacterial and fungal contaminations are usually easy to detect in culture medium due to changes in pH and visual indicators such as color and opacity. Mycoplasma contamination has been detected in 15–35% of cell lines deposited in some cell culture collection. This is because mycoplasma contaminations often cause little changes that can be readily detected by visual inspection. However, bacterial, fungal, and mycoplasma contamination can be more effectively controlled than viral contamination by careful screening of initial parental cell banks, proper environmental monitoring, along with ongoing testing…

Cell & Tissue Banking

In recent years, cell therapy has been suggested as a promising approach for repair and regeneration of damaged tissues. VesCell™, 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 CD31…

Cell & Gene Therapy Manufacturing Uncategorized

Many precautions are taken in a typical research lab to ensure the integrity of biological specimens. Temperature, storage, and personnel access, among others, are all tightly controlled, and codified into standard operating procedures (SOPs), if not almost biblical law. And no wonder — companies have millions invested in biotech solutions whose progress is often measured in years and decades. Scientists have their life’s work on the line. So, it is with some surprise that the diligence most companies exercise during the research and development process is not always maintained during specimen transport. Every time a specimen leaves the lab, be it for further analytical testing or investigational purposes, it runs a heightened risk of contamination, especially from fluctuating temperatures. Ensuring that this does not happen should be the responsibility and concern of everyone with a stake in a biological product’s success…

Research Risk Analysis and Management

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

The Lentiviral Vector Reference Working Group (LVRWG) was created at the conclusion of a meeting organized by The Williamsburg BioProcessing Foundation in June 2002, in conjunction with the American Society of Gene Therapy (ASGT) annual conference. The meeting participants were gathered to evaluate the need for developing reference material to ensure comparability of lentiviral and retroviral vectors, in a similar spirit to the Adenovirus Reference Material program that had just been completed. The concensus at the conclusion of this meeting was that the diversity in the lentiviral vector field, which includes vectors derived from different parental viruses and with various designs, does not allow for identification of a single reference material that would benefit more than a single or very few investigators…

Viral Reference Materials Viral Vectors

Acute Renal Failure (ARF) is a severe inflammatory disease state often accompanied by multiple organ failure (MOF). ARF is precipitated by many factors such as blood loss, surgery, sepsis, toxins, trauma, and is most often linked to the loss of kidney tubule function. Proximal tubule cells are specifically injured in acute renal failure. Current therapies for ARF involve conventional kidney support with hemodialysis or hemofiltration. These therapies offer replacement of normal renal functions such as waste removal, fluid, and electrolyte balance, but they cannot provide vital endocrinological and metabolic functions of a healthy kidney. Despite advances in synthetic materials and extracorporeal circuits for hemodialysis and hemofiltration, ARF is associated with a high mortality rate ranging between 55–70 percent…

Cell & Gene Therapy Risk Analysis and Management

A prerequisite for producing medicinal products is ensuring their quality and safety. This requires appropriately controlled and standardised manufacture and testing procedures that result in consistent potency, safety, and efficacy. Assuring the quality and safety of gene therapy products in particular presents a great challenge because they are cell-based, multi-gene products which include viral and therapeutic proteins as well as modified cells. Although more than 860 gene transfer clinical trials are in progress and the first gene therapy product is already on the market (in China), the development of reference materials for gene therapy products is at an early stage with only a few accessible reference materials. Standardisation of gene therapy products to ensure their quality and safety is clearly necessary and has become increasingly important. Standardisation and other issues specifically related to gene therapy products are discussed in this article…

Cell & Gene Therapy Viral Reference Materials

Validating the safety of biological preparations requires thorough testing for contamination by adventitious agents. Utilizing mammalian cell cultures to produce recombinant proteins as biopharmaceuticals requires testing for viral contamination. The polymerase chain reaction (PCR) may be employed to specifically detect the presence of viral DNA or RNA with great sensitivity. PCR assays are particularly useful for the qualification of recombinant cell banks. Regulatory agencies recommend that mammalian cell banks be tested for a variety of possible human viral contaminants. In most cases the cells used to produce the cell bank have been previously analyzed for viral contamination. The use of PCR for the detection of viruses in the final banked cells can alleviate the need for difficult, costly, and time-consuming infectivity assays. In some cases the relevant viruses cannot be cultured, eliminating the ability to perform infectivity assays. The PCR assay can provide a sensitive and specific method for detection of viral contamination when standard infectivity assays are unsatisfactory…

Cell & Tissue Banking

On January 31, 2003, FDA under the leadership of Commissioner Dr. Mark McClellan, issued a report entitled “Improving Innovation in Medical Technology: Beyond 2002.” One of the goals described in this report is to “speed potentially important emerging technologies to the market by reducing regulatory uncertainty and increasing the predictability of product development.” The technology areas of cell therapy and gene therapy were specifically identified. This article highlights some of the challenges for manufacturers and regulators of these products and describes ongoing efforts at FDA — as well as opportunities to partner with FDA — to improve the product development process for cell therapy and gene therapy products…

Cell & Gene Therapy Manufacturing Regulatory