The Technograph

Drug discovery and development is a risky business.  Every drug available to patients today traveled a long road and is one success story out of thousands that did not make it.

According to Wanda Haschek-Hock, professor of veterinary medicine at the University of Illinois, it takes many years and up to billion dollars to take a single drug from initial discovery to the market. 


“The discovery phase is followed by drug development, which includes safety testing in animals,” Haschek-Hock said.  “Then the drug goes through the approval process from the regulatory agency, the Food and Drug Administration, before going into clinical trials in people.” 


If the drug succeeds, it will be marketed and may be sold around the world.  However, if the drug has toxic side effects or does not efficiently treat the disease, it will be pulled from development.

According to Hakim Djaballah from the Sloan-Kettering Institute, it all begins when a drug candidate is identified. This can happen in one of two ways: A compound serendipitously found to have certain pharmaceutical properties can be developed into a treatment, or a specific target in a diseased cell can be identified and a compound that binds it to restore normal function can be sought out.

As the director of the high-throughput drug screening facility at Sloan Kettering, Djaballah's work focuses on the latter. Prior to the development of new technologies in the 90's, drug screening was time-consuming and required extensive syntheses and individual testing of compounds. Now, with developments in robotics and combinatorial chemistry, it is possible to screen thousands of drugs at a time, shortening the time it takes to discover drug candidates.

Once a “lead” compound is chosen, the Food and Drug Administration requires testing on animals to see if toxic side effects exist, according to Mike Biehl, professor of toxicology at the University of Illinois. Concurrently, drug formulations are developed to enable absorption into the animal's system.

Unexpected toxicity issues oftentimes arise during animal studies, requiring the drug, once again, to be pulled from development.

  “The first time you're going to high doses in animals [you] oftentimes will discover some sort of toxic issue that you didn't anticipate,” Biehl said.

If testing in both a rodent species and a large animal species is successful, the company may apply for FDA approval to test in humans, although success in animals does not guarantee success in humans.

“If it works in a mouse, and it works in a dog and it works in a monkey, there's no guarantee it will work in a human patient,” Djaballah said, explaining that the discrepancy is due to genetic differences between humans and other animals.

During clinical trials, the drug will be administered to humans, starting with healthy volunteers in Phase I, and progressing to patients with the disease in Phases II and III.

“Once you get to Phase II, that's when you're trying to assess the efficacy of the drug in real patients,” Biehl said. Then, in Phase III, studies are performed in patients around the world, to see if the drug is going to work with the same level of efficacy and safety in people of different cultural descents.

Phase I and II are performed in a few hospitals with hundreds of volunteers, Biehl said. By the time the drug gets to Phase III, hundreds of thousands of patients in hospitals around the world are being tested.

All the hurdles involved in the process may explain why so few compounds successfully make it from the lab bench to the hospital bedside. With the high costs involved, it may now be clearer why pharmaceutical companies charge as much as they do for the drugs that do get marketed.

Biehl told the story of a drug, Torcetrapib, which made it all the way to Phase III and cost the company nearly a billion dollars before it was pulled for being correlated with increased cardiac events, showing that failed drugs can cost the company a lot of time and money.

The future of drug discovery will be paved by advances in the fields of bioimaging, nanotechnology and the “-omics” (genomics, proteomic, metabolomics), Biehl said. Many researchers are striving toward the goal of “'personalized medicine', the idea that future therapies, both preventative and curative, will be based on our own individual genetic fingerprint.”

“The medication will be prescribed based on medical needs,” Waschek-Hock said. As research continuously progresses, personalized medicine will one day allow patients' therapies to be tailored to their specific needs.

With this end in mind, researchers in drug discovery and development continuously strive toward the goal of bringing new treatments to the market, overcoming the numerous challenges along the way. 

Tagged with: Drugs, drug discovery, fda