What really is involved in developing a new drug?

    The purpose of this article is to look at how drugs are developed today in the modern world and how the chemical engineer is instrumental in the development of new drugs.  Let's first take a look at how the development of a new drug begins.  It is interesting to also know that on average it takes 12 years for an experimental drug to travel from the lab to your medicine cabinet.  Only 5 in 5,000 compounds that enter the preclinical testing phase actually make it to human testing.   One of these five drugs tested in people is approved.  As you can see it is a rigorous and costly process that must be followed to get a new drug to your medicine cabinet.  It is estimated on average a company may spend $300 to $400 million dollars to get just one drug to your medicine cabinet.  It is not hard to see why some new medicines on the market are so expensive.  Let's take a look at the steps involved in developing a new drug.

Preclinical Testing         

     This is the initial phase of the testing that begins in the laboratory.  A pharmaceutical company will conduct studies in the lab and on animals to show the biological activity of the compound against a targeted disease. The compound is then evaluated for safety.  These tests take about 3 1/2 to 4 years to complete.   The chemical engineer would be heavily involved in this phase of  drug development.

Investigational New Drug Application (IND)

    After the above preclinical testing is completed the company then files an IND with the FDA to begin testing the drug in people.  The IND will become effective if the FDA does not disprove it within 30 days. The IND will show results of previous experiments, how, where and by whom the new studies will be conducted.   The IND also looks at the chemical structure of the compound, how it works in the body, and any toxic effects found in the animal studies. The IND will also look at how the compound is manufactured.   The IND must be reviewed and approved by the Institutional Review Board where the study will be conducted, and progress reports on clinical trials must be submitted at least annually to the FDA.

Clinical Trials, Phase I, II, & III

After the IND has not been disapproved within 30 days, then the next phase of testing begins, which is the clinical trials.

Phase I   This phase of the testing takes about a year and involves about 20 to 80 normal, healthy volunteers. The tests study a drug's safety profile, including the safe dosage range. The studies also determine how a drug is absorbed, distributed, metabolized and excreted, and the duration of its action. 

Phase II  In this phase, controlled studies of approximately 100 to 300 volunteer patients (people with the disease) assess the drug's effectiveness.  This phase normally takes about 2 years.

Phase III  This phase involves 1,000 to 3,000 patients in clinics and hospitals. Physicians monitor patients closely to determine the efficacy and identify adverse reactions. This phase lasts about three years. 

New Drug Application (NDA)

  After all of the clinical trials mentioned above are completed, then the company analyzes the data and files an NDA with the FDA if the data successfully demonstrates safety and effectiveness. The NDA is usually about 100,000 pages or more and contains all of the scientific information that the company has gathered. By law, the FDA is allowed six months to review an NDA.  In most cases the time from first submission of an NDA and final FDA approval usually exceeds six months. The average NDA review time for new molecular entities approved in 1992 was 29.9 months.

Approval

   Once the FDA approves the NDA, the new medicine becomes available for physicians to prescribe.  The company must continue to submit periodic reports to the FDA, including any cases of adverse reactions and appropriate quality control records.  The FDA requires some medicines to have additional studies (Phase IV) to evaluate the long-term effects of the drugs.

      After reading the above steps in the development of a new drug, it is not hard to see why drugs cost so much when they finally do get to our medicine cabinets.  Many people in the pharmaceutical industry   are looking for ways to expedite the development of drugs and to decrease some of the money put into this development.  One resource that is being utilized in the development of new drugs is bioinformatics.  The Bioinformatics industry is still in its infancy stages, but it has started to change the way drug development has emerged since 1998.  Bioinformatics helps to take some of the fragmentation out of the development of new drugs.  Most drug development has been more or less by trial and error.  Bioinformatics uses information technology to be able to develop large databases and algorithms which help in the development of new drugs.

     An example of this is the European Bioinformatics Industry (EBI).  The EBI serves researchers in molecular biology, genetics, medicine and agriculture from academia.  The EBI also serves the agricultural, biotechnology, chemical and pharmaceutical industries.  The EBI is able to serve these researchers and industries by building, maintaining and making available databases and information services that relate to molecular biology.  The EBI also carries out research in bioinformatics and computational molecular biology.  More information about EBI can be obtained from going to their website which is as follows: http://www.ebi.ac.uk/Information/index.html  

     For those of you who are interested in learning more about the pharmaceutical pipeline (an industry term used for the research and development process of creating new drugs), Searle's Research and Development Department has a web site for you.  This web site actually takes you step by step in the development of a new drug.  The web site is as follows: http://www.searlehealthnet.com/pipeline.html   On this web site you can select from a few diseases such as cancer, cardiovascular related diseases, or arthritis as your primary target to be able to develop a new drug for. 

    If the virtual formulation of a new drug is not enough, then all of you are invited to visit the following site from John Hopkins University, in which you can actually be the participant in a research study.  Most of these studies involve the development or refinement of drugs but some don't involve any drugs at all.   There is also a monetary incentive involved with some studies.  The web site is as follows:  http://www.jhbmc.jhu.edu/studies/index.html   Due to geographic limitations, it may be difficult to be able to attend the clinic visits that are required.  To be able to find out research studies in your local area, check with the nearest teaching/university based hospital and I am sure they would be more than happy to get you involved in a research study.

    In summation, it is easy to see the vital role that chemical engineers play in the development of new drugs.  It takes the knowledge and skill of many disciplines to formulate a new drug.  When all of these   discipline work together, it helps to expedite the formation of new drugs to help alleviate the effects of diseases for people around the world.