By: Arzoo Zaheer
Date: May-18-08
Improving Efficiency
To elminate R&D bottlenecks, drug companies are evaluating all phases of discovery and development and are using novel approaches to speed them up.
By: Stu Borman
Over the past decades, there have been many breakthroughs in the discovery and development of new medications to treat diseases. Yet a number of devastating human ailments still cannot be treated effectively with drugs. Cancer, autoimmune diseases, circulatory conditions, neurodegeneration, and other ills continue to resist medicinal intervention to one degree or another.
Researchers in academia, government, and the pharmaceutical industry wage battle against these diseases and win many victories. But questions have been raised about whether their efforts are as effective as they could be. Has the efficiency of drug discovery anddevelopment slipped? If so, how can the process be improved? Many people are endeavoring to answer these questions.
Data indicate that the productivity of the pharmaceutical industry has slipped in recent years. A study last year (J. Am. Med. Assoc. 2005, 294, 1333) showed that U.S. biomedical research funding (adjusted for inflation) rose from $48 billion to $94 billion over a decade beginning in the early 1990s. “That’s a major increase in investment,” says Food & Drug Administration Deputy Commissioner for Operations Janet Woodcock, but “the curve of submissions of new drugs and biologics to FDA is in the opposite direction, almost a mirror image of the investment curve.
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In this article, the author Stu Borman discusses advances that have been made in the pharmaceutical industry to ensure efficient Research and Development procedures. The article proved really informative since it walks the reader through all steps of the development of a medicinal compound, while pointing out different crucial procedures that have been developed to ensure efficient and accurate discovery of the drugs. Although the pharma company is investing a lot of money into finding therapeutic molecules the total number of NDAs that are being submitted to the FDA is actually declining. There is a lower productivity rate prevalent all over the world while the investments and developments costs are increasing. The only solution to this problem according to Borman is to ensure that the pharmaceutical company continues to use novel and modern drug development processes while incorporating new scientific technology in their processes. In March 2006, FDA started an initiative known as Critical Path Initiative (CPI) that seeks to find different ways of modernizing the drug development process.
The article goes on to identify several ways of improving R&D process. While finding the proper medicinal compound, Borman argues that it’s best to use a combination of approaches and not just one. For instance, the popular reductionist approach is very helpful in identifying a protein in relevance to a disease by screening to find the proper compounds that interact or modulate with it. However, Borman notes that this approach has limitations. For instance, certain drugs whose discovery depend on studying the actual biological systems such as type 2 diabetes couldn’t have been discovered with the reductionist approach.
When it comes to drug validation, Borman again identifies a couple of methods such as Knockouts organisms and System Biology. Borman points that lead optimization is a critical issue to be kept in mind while designing a drug. Several novel methods such as computational approach, bioinformatics, computer modeling and fragment based approach are mentioned.
It’s curious to note that most of the drugs that pass phase 2 end up failing phase 3 due to safety concerns. Hence a lot of money, time and resources are wasted. According to Boremen, this can be avoided if one uses Microdosing. Sometimes referred to as phase zero, microdosing involves giving the subjects extremely low doses to see the pharmacokinetic effects of the drug. The author sounds really hopeful that in the future better tools will be developed to ensure speedy and more efficient drug research and development.
In my opinion, this article does a great job in identifying novel approaches that would ensure speedy drug development. I was quite disappointed to see that Boreman did not mention proteomics at all. From my understanding, proteomics is one of the most efficient ways of drug discovery. Techniques such as : 2D Page, IPG, NEPHGE, HPLC, CE, Protein Chips, Isotope Coded Affinity Tag Technology (ICAT), Electroscopy Ionization (ESI), Matrix Assisted Laser Desorption Ionization Mass Spectroscopy (MALDI-MS) are used to perform large scale studies of the drugs. A market report generated by Research and Markets show that using proteomics would decrease the drug development time by three years and would double the number of successful NDAs. Furthermore, the R&D costs were shown to have been reduced by 30% per year.
Another new field that would greatly assist in lead optimization, decreasing the cost of drug development, reducing the risk of late clinic development failure and monitoring of clinical candidates is chemogenomics. It`s pioneered by Iconix Pharmaceuticals and is designed to enable pharmaceutical companies to increase the odds of advancing the correct medicinal compounds to the clinic while managing R&D of these drugs in human testing. You may purchase this report “Chemical Genomics – Commercial Applications in Drug Discovery and Development“.
One fundamental challenge that the pharmaceutical industry is currently facing is that a large proportion of the drugs actually fail in development owing to poor pharmacokinetics. Studies have shown that the major cause of dropping research subjects during development are the compounds pharmacokinetics (PK) or its ADME. Most of the time, it’s the polymorphic metabolic pathways, highly variable absorption rate, and critical drug interactions that are poorly misunderstood. Hence there is an increased need to thoroughly study the pharmacokinetics factors governing absorption, distribution, metabolism and excretion (ADME), something that is not always comprehended with full certainty. One way of studying ADME would be to administer radiolabelled drug to the subjects so that it’s possible to mark the progress of the metabolites throughout the body. Once the radiolabel drug is in the body of the subject, its possible to monitor the activity of its metabolites by using Accelerated Mass Spectroscopy (AMS), which is highly sensitive technique to detect carbon-14. Kindly read this article for more detail on this issue.
In conclusion, managing R&D bottleneck to improve drug development efficiency, the scientists must continue to discover and collaborate upon critical methods that would assist in lead optimization, proper target validation, drug designing and creating the correct medicinal compound. I would end by stating that collaboration and communication with peer pharmaceutical companies is a key factor in ensuring that drug and research development processes reach the desired efficiency in the future.
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