General Articles

Christiane von Ludwig
EJHP•3/2004

Abstract

In this work, we examine the way in which stability information obtained from studies o­n small model peptides correlates with similar information acquired from a protein. The rates of deamidation, oxidation, and diketopiperazine reactions in model peptide systems were compared to those of recombinant human vascular endothelial growth factor (rhVEGF). The N-terminal residues of rhVEGF, a potent mitogen in angiogenesis, are susceptible to the aforementioned reactions. The degradation of the peptides L-Ala-L-Pro-L-Met (APM) and Gly-L-Gln-L-Asn-L-His-L-His (GQNHH), residues 1-3 and 8-12 of rhVEGF, respectively, and rhVEGF were examined at pH 5 and 8 at 37°C. Capillary electrophoresis and high-performance liquid chromatography (HPLC) stability-indicating assays were developed to monitor the degradation of the penta- and tripeptides, respectively. The degradation of rhVEGF was determined by tryptic mapping and quantified by RP-HPLC.

Science deserves all the credit it gets, and more, for driving this industry. Still, no science succeeds without a certain application of what we broadly call art. Inside the scientific discipline, many arts apply-the art of experiment, the art of planning, and the art of free association among them. Although the human brain invented science, it has never surrendered fully to its constraint. That may be because o­ne lobe wants to embrace the discipline, and the other wants to fight or flee it. However much we depend o­n the mathematical rigor of the scientific mind, we cling to the mysterious spontaneity of the human imagination.

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According to pharmaceutical scientists, all contemporary drug therapy is based o­n a total of 500 targets. Recent advances in genomics and proteomics promise a quantum leap in usable drug targets, but pharmaceutical and biopharmaceutical companies are in a bind when it comes to validating targets and optimizing leads. This has created a market for outsourced drug discovery chemistry.“The most significant change in medicinal chemistry can be traced to the genomic revolution,” said David Coffen, Ph.D., the chief scientific officer of Discovery Partners International (DPI). “Before, the medicinal chemist focused around a particular therapeutic area. Now, he or she is more likely to be an expert in target classes.” For example, the skills for finding HIV/AIDS protease inhibitors can be used for other inhibitors in such areas as heart attacks and Alzheimer’s disease. “It’s led to a new breed of chemist,” Dr. Coffen added.

The early bird may get the worm, but it has little chance of competing in the technologically explosive world of neurological biologics. The bird hatched from its shell with the worm gripped firmly in its beak is the o­ne that will survive and be successful. With some of world's most desperate patients looking to the industry to cure a host of devastating conditions, effective marketing strategies and communications plans must be hatched during research.The experts agree that the super-customized treatments of the future will make blockbusters a thing of the past. All in all, the top ten marketing challenges facing any company planning to license, manufacture, or distribute any of the most exciting therapies in neurology cannot be ignored. They're o­n their way-ready or not.

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Today, more and more Original Equipment Manufacturers (OEMs) in the pharmaceutical and biotechnology fields are turning to Contract Equipment Manufacturers (CEMs) to manufacture their products; particularly those who use drug delivery technology. Typically, a drug delivery company will develop the product and then also manufacture it o­nce it reaches commercialization. This article takes a look at the implementation and reality of manufacturing supply arrangements between these OEM companies and a drug delivery company with manufacturing capabilities.

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A discussion of the validation and operation of two commercially available vapor-phase hydrogen peroxide decontamination systems is presented, based o­n a hands-on examination of both systems.

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Abstract

The penetration of paclitaxel into multilayered solid tumors is time- and concentration-dependent, a result of the drug-induced apoptosis and changes in tissue composition. This study evaluates whether this tissue penetration property applies to other highly protein-bound drugs capable of inducing apoptosis. The penetration of doxorubicin was studied in histocultures of prostate xenograft tumors and tumor specimens obtained from patients who underwent radical prostatectomy. The kinetics of drug uptake and efflux in whole tumor histocultures were studied by analyzing the average tumor drug concentration using high-pressure liquid chromatography. Spatial drug distribution in tumors and the drug concentration gradient across the tumors were studied using fluorescence microscopy. The results indicate that drug penetration was limited to the periphery for 12 hours in patient tumors and to 24 hours in the more densely packed xenograft tumors.

Following what he refers to as "a very smooth leadership transition," Amgen's new chairman and CEO Kevin Sharer is shaking things up. In January, he created two new executive vice-president positions and went outside the company to fill them. In May, he made room for a third new vice-president, a dot-com refugee with no pharma background. That same month, he raised the wholesale price of Epogen (epoetin alfa) 3.9 percent, generating criticism from dialysis centers. And in an earlier surprise move for the independent biotech, he initiated the purchase of Kinetix, a small-molecule company 3,000 miles from headquarters.

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