The main objective of the FDA is to protect public health by ensuring the safety and efficacy of all drugs available to consumers. The FDA was explicitly given the authority to monitor and regulate marketable drugs in the Federal Food, Drug and Cosmetic Act of 1938. This law was enacted in response to more than 100 deaths resulting from consumption of an untested drug known as "Elixir Sulfanilamide". This was the first time in U.S. history that drug manufacturers were required to test drugs, in order to provide evidence that the drug was safe, before it could be made available to the general public.
Who reviews the results of this testing?
- Chemists - review the formulation of the drug and evaluate the manufacturing process to ensure the integrity of the drug
- Pharmacologists - evaluate the effects that the drug has had upon animals in animal testing
- Physicians - evaluate the effects, both good and bad, that were found as a result of the drug in clinical trials.
- Pharmacokineticists - determine how effective the active ingredient in the product is in its uptake into the body and elimination from the body.
- Statisticians - evaluate data generated from studies
- Microbiologists - review drugs that act upon microorganisms in the body and also review drugs that contain microorganisms
Benefits and Priorities of the FDA
"CDER's mission is to promote and protect the public health by ensuring that safe and effective drugs are available" (FDA, 1999).
Benefits:
A) Universalized standards that require the results of well-controlled studies to provide substantial evidence of a drug's effectiveness, while showing that the product is safe under the conditions of its proposed labeling. All drugs undergo the same rigorous tests and procedures.
B) Gauges effectiveness by ensuring that a drug's benefits outweigh the known risks. They even monitor the use of marketed drugs for unexpected health risks.Priorities:
A) Give Proof of a Drug's Safety and Effectiveness (refer to section entitled "Benefits")
B) Get Drugs on the Market Quickly
C) Chemical Type and Potential Benefit - All drugs that offer a significant medical advancement over existing therapies for any disease are considered priority drugs.
(FDA, 1999)
Laboratory and Animal Studies
The FDA plays a very small role in the early stages of drug development. The one and only responsibility of the FDA is to ensure the safety and efficacy of the final drug product. The research and development of drugs that takes place prior to FDA approval is left entirely to the drug manufacturers. The FDA does not become involved in the drug development process until after all laboratory and animal testing is completed and the drug companies are seeking permission to begin clinical testing on human subjects. At this time, the FDA reviews the results of the lab and animal testing and decides whether to grant approval for this next step - human clinical trials - for which the FDA has established many strict guidelines.
Every year thousands of compounds are tested to determine their potential medicinal benefits. Of these thousands of drugs, most are abandoned or fail after animal testing. It is estimated that only 5 in 5,000 drugs that complete animal testing ever reach clinical trials in humans and then, only one in five of these drugs will be granted final approval by the FDA after all testing has been completed. The FDA estimates that it takes approximately eight and a half years of testing and research on behalf of a drug company before a drug can be approved and put on the market. Each new drug will cost somewhere in the vicinity of 359 million dollars to develop. Although there is no standard route for drug development in the U.S., almost all drug development begins with the study of the function of biochemical pathways within the body. By gaining an understanding of these pathways, scientists can determine the cause of disease or dysfunction and attempt to develop a drug that can intervene at the necessary point in the pathway to correct or avoid the problem. Because there are so many facets of drug research, many specialists - including organic chemists, physiologists, biochemists, molecular biologists, statisticians, toxicologists, pharmacologists, and computer scientists - are involved in the development process. The advent of high tech computer software and the assistance of computer scientists have changed the face of drug development. Research can now be greatly expedited through the use of computer simulations showing drug action in the body at the cellular level.
When testing finally moves from the laboratory setting to animal experimentation, it is crucial that multiple species of the animal in question be tested. This is important because a single drug can affect different species in a very different manner. Animal testing is also critical because it can illuminate possible side effects that are manifested as a result of the drug. Testing in animals also serves as a means through which dosage can be determined. Scientists must also determine the amount of active ingredient in each drug that enters the blood, how quickly this ingredient is absorbed by the body, the mechanism through which this substance is broken down, whether this compound has any toxic byproducts, and how quickly these byproducts are eliminated from the body, before the drug can be tested on human subjects.
(FDA, 1999)
Testing Drugs in People:
Phase I Testing:
Phase I testing is performed on a small number of healthy volunteers or patients. Through Phase I testing, the institution assesses acute adverse effects of the drug and the safest dosage that does not produce side effects, and begins to clarify exactly how the drug affects people.
Phase II Testing
Phase II marks the beginning of observations of the drug's effectiveness. The drug is given to people who have the condition that it is meant to treat. Controls are introduced, wherein test subjects are given either a placebo, another known effective drug, or the drug in question at a different dosage. Phase II usually involves several hundred test subjects.
Phase III Testing
The intention of Phase III testing is to gain additional information about the drug's safety and effectiveness. It involves the same use of elaborate controls as Phase II testing. This phase provides researchers with the ability to extrapolate data to a larger portion of the population. Several hundred to several thousand test subjects are used in this phase.
New Drug Application Review, Post-clinical Portion
The FDA reviews the manufacturer's claim that the product is safe, and evaluates the overall clinical testing results. FDA reviews the product's proposed label to see if it fits standard labeling requirements. FDA inspects the product's manufacturing facility and clinical trial sites to evaluate procedures and results, and collects samples for FDA lab work. A final decision is made. Signed approval by a division director legalizes a product to be released to the public.(FDA, 1999)