Drug Discovery and Approval Process

James Gallagher English 202C

What is Drug Discovery? Drugs and pharmaceuticals are used every day, whether it is to treat a simple cough or something more complex, there is a rigorous process a drug must go through in order to be approved for use by the public. This process is known as Drug Discovery and is a very long and complicated process that every drug that is used on the market today has gone through. It includes multiple levels of checks and balances to ensure the only the safest drugs make it through each section of the process. If the drug passes the discovery portion it is then developed into a drug and marketed. With any compound that is taken within the body, there is an effect exhibited within the organism. This process is to determine at what dose level and with what compounds or medications will give the therapeutic effect that is being desired. If a toxic effect is shown then this drug is either not good at that particular dose or the toxicity is too great to give to the public as a therapeutic. This process is a 5-10 year process and is very expensive, this is in place to ensure that drug companies do not just flood the approval process in the hopes that one drug will get through.

Discovery and Target Determination This portion of the process is to first find what the disease or affliction is, once this is determined than the mechanisms of the disease are looked at. In the beginning of the discovery process there are between 10,000 to 20,000 drug candidates, after testing these drugs in vitro, a target is determined. A target is usually determined by seeing what the disease mechanism acts on and if the drug can inhibit that process or block the disease activity and the drugs that either exhibit toxicity or do not act on the target are removed from the process,. The remaining drugs are then optimized to be tested on animals and other trials. It is very important that only the best drugs are chosen at this juncture for that is what is needed. Development and Production The next portion of the Drug Discovery process is the development of marketable drugs for use. The drugs that passed the initial discovery process are in this stage of the process. This portion is where a majority of the toxicology testing is done, these tests are done on animals such as mice, rats, and pigs. There is also testing on the toxicological principal known as ADME which stands for absorption, distribution, metabolism, and excretion. These drugs are assayed to see where the drug acts, where it goes, how it is metabolized, and how it is then taken out of the body. If a drug does not have favorable ADME it is taken out of the process. A part of the reason why this process takes so long is that the toxicity testing has to be done on different levels such as acute or chronic testing which could take anywhere from weeks to years. The drugs that pass this section of the testing are then put on preliminary human safety and dose response assays. It is not uncommon for a majority of the drugs who reach this step to fail and are taken out of the process. The drugs are tested on non-target populations and are closely observed for any type of adverse effect. The next step is to test on the target population to determine absolute safety and efficacy of the drug. If by these point the drug has shown limited toxicity and good therapeutic effects the drug is approved by the NDA and is registered and marketed.

Post-market Surveillance Even though a drug has been approved for use the drug is still under scrutiny by many organizations to see if there are any undesirable effects. Unfortunately it is fairly common for a drug that passed all of the tests during the initial testing process to suddenly give severe if not fatal side effects. Once this happens the drug is pulled from circulation, usually the company has to pay millions of dollars in law suits and the process needs to start all over again. This is still an

important part of the process because no company wants to have a fatal drug out in circulation, if a drug does not cause any unexpected toxicity or side effects than the drug is made until it is no longer needed by the populace. The Process Brought Together The Drug Discovery process is integral in creating safe and effective drugs. If these compounds are not put through such rigorous testing than a drug that is easily toxic or fatal could enter the public market. The process is made to be long and expensive to make sure only the best drugs are put through and are used. If a drug fails at all during any step the drug is pulled from the process and is not used. Even drugs that make it all the way through to be approved and used can still have catastrophic side effects that need to be addressed as soon as they happen. This process is a time-tested and effective way of testing and developing effective drugs and is the best way to determine which compounds are best for the disease or affliction they need to act on.