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…
Tag: <span>characterization</span>
Since the mid-1970’s, when Kohler and Milstein first discovered the process by which myeloma cells and splenocytes could be fused to produce monoclonal antibodies (MAbs), a whole new world of important therapeutic, prophylactic and diagnostic products has opened up, bringing in huge benefits for patients and manufacturers. The total sales of therapeutic MAbs reached more than $13 billion in 2005. Sixteen of the 18 FDA-approved MAbs came to the market after 1997, and over 150 are currently in clinical development, suggesting their increasing medical importance and the remarkable, recent advancements in development technology…
As human immunodeficiency virus type-1 (HIV-1) continues to spread around the world, scientists are actively pursuing effective vaccines against the infectious disease that results in AIDS. A number of vaccine designs have been developed, including plasmid DNA constructs encoding HIV proteins. One advantage of DNA vaccination is that after the uptake of the plasmid by the host cells, the encoded antigens are expressed in the native conformation and allow authentic immunological processing of the antigen. Another advantage of DNA vaccines is that they can be repeatedly administered without vector-directed immunity limiting the efficacy of the boost. DNA vaccines alone can induce both humoral and cellular immune responses and provide modest protection against disease progression in the preclinical, nonhuman primate model when challenged with simian immunodeficiency virus (SIV)…
The United States Pharmacopeia (USP) is a not-for-profit nongovernmental organization founded in 1820 that develops public standards for drug substances and products; these standards are enforceable by FDA and have been adopted by many nations around the world. USP General Chapters provide industrial and academic researchers alike with crucial guidance, particularly in areas where there is a regulatory void. A good recent example is the proposed USP general information chapter…
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’t make it through pre-clinical development, or which entered clinical trials and failed for any number of reasons…
At the onset of modern-day biotechnology, products typically fell into two distinct categories, the traditional high volume, low value products (e.g. beer and industrial enzymes) that had come to characterize the biotechnology industry, and low volume, high cost products. Recombinant proteins, the result of technological advances in molecular biology, have come to typify these latter products. Recombinant protein therapeutics have been hugely successful, potentially outstripping production capacity and continue to drive much of the biotechnology. Meanwhile, many recombinant proteins, those characterized as research tools and reagents, are governed by a price-volume relationship typical of industrial enzymes. In a competitive environment, they are fast becoming commodities — price sensitive, packaged as kits, coupled to instrumentation, and relying on heavy marketing and brand recognition. Ominously, the advantage protein therapeutics have enjoyed with patent protection and regulatory constraints on production is being threatened as patents expire and competition from generics increases…
Cation exchange chromatography (CEX) is a versatile method for separation of proteins based on exploiting differences in positive electrostatic charges. In CEX, proteins are bound to the negatively charged stationary phase (cation exchangers) and then eluted using a salt gradient. Typically, the liquid-phase pH in CEX is lower than the isoelectric points (pI) of the proteins. CEX has been used to monitor various post-translational modifications such as glycosylation, deamidation, phosphorylation, truncation, oxidation, C-terminal and N-terminal clipping, and N-terminal cyclization. Some of these variants may exhibit different bioactivity. Therefore, it is important to characterize protein variants and monitor the stability of these variants throughout the process of drug discovery, development, and manufacture. Characterization of complex proteins such as antibodies, has traditionally been performed using slab gel-based techniques such as isoelectric focusing (IEF). This technique is qualitative and time consuming. It also generates large quantities of chemical waste from the staining process…