Tag: <span>FDA</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

Recombinant adeno-¬≠associated viral (rAAV) vectors have proven to be efficient vehicles for gene transfer in animal models. The attractive features of this vector system are long-term gene expression with little or no associated toxicities following administration to a variety of tissues. Previous and ongoing clinical trials in humans demonstrate a very good over-all safety profile. However, one of the caveats of this work that has been carried out by several ¬≠laboratories is the inability to normalize vector doses administered by different investigators to animals and humans. Most of the work to date has involved AAV serotype2 vectors, but vector systems based on other AAV ¬≠serotypes are being rapidly developed…

Viral Reference Materials Viral Vectors

Manufacturers of biological products have come to accept that it makes sense, from both a business as well as a regulatory perspective, to address GMP compliance issues with bioprocessing methods as early as possible in product development. Logically, this same reasoning would also apply to the associated analytical methods used to characterize the product; however, companies still frequently leave methods optimization and validation until later in the developmental timeline which can expose them to unexpected regulatory challenges. In addition, as therapeutics increase in complexity (e.g., cell therapies, transgenics), it raises the likelihood that product characterization will be assessed by novel and increasingly intricate assays‚ÄĒmaking it difficult to follow a ‚Äúone size fits all‚ÄĚ approach to method selection, development and validation‚Ķ

Manufacturing Regulatory

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 criteria…

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

New regulatory initiatives often produce paranoid responses. These over-reactions are often a result of initial rumors fueled by less-than scrupulous consultants or by misinterpreted statements reported out of context from unscripted regulators. The ‚Äúremote monitoring capability‚ÄĚ incorporated into the emerging Process Analytical Technology (www.fda.gov/cder/OPS/PAT.htm) initiative is a prime example. Put the fear back in the closet: remote monitoring will not lead to unannounced or secret FDA electronic visits, unscheduled remote audits, or regulatory spying on industry processing activities…

Regulatory

Although biological products are being licensed at a fairly steady pace, the cost to develop each product can be incredibly high, and far too many products with very little chance of success are entering clinical trials. The cost of developing a biological product is now estimated to be as high as $1.7 billion. This is truly a staggering figure that would seem to prevent all but the strongest company from attempting such a gamble. However, this number includes the cost of all the products that didn‚Äôt make it through pre-clinical development, or which entered clinical trials and failed for any number of reasons…

Biologics Production Regulatory

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 ‚ÄĒ as well as opportunities to partner with FDA ‚ÄĒ to improve the product development process for cell therapy and gene therapy products…

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

As development proceeds for adenoviral vectors in gene transfer clinical trials, it becomes increasingly important that these products demonstrate a good safety profile, and thereby build confidence in those who must make decisions about risk/benefit ratios, dose escalation, and efficacy. Currently, safety and efficacy are based predominantly upon the analysis of data generated by non-standardized methods, resulting in inconsistent values being reported for virus titer and particle counts…

Risk Analysis and Management Viral Reference Materials