US Drug Approval Process

How much time and money does it take to bring a drug to market in the United States?  According to FDA estimates, it takes an average of 8 ½ to 17 years, from drug conception to marketing, before a drug is finally FDA approved for use in the general patient population.  An article published in Health Affairs (1996) estimated the cost of brining a new drug to market as being between $500 and $2,000 million.  But before a drug (chemical) may undergo human testing towards drug approval, pre-clinical research must be conducted.  In pre-clinical research, the chemical being considered for medical use is synthesized and purified and is subjected to animal testing. Animal testing is necessary so that the pharmacokinetic and pharmacodynamic parameters, toxicities and metabolites may be assessed and evaluated.  The FDA and the drug company evaluate the preliminary data to determine whether it is appropriate for testing in human subjects.  If the chemical is deemed safe for testing in human subjects by the FDA, clinical study protocols are written by the drug manufacturer and are approved by the Institutional Review Board (IRB) before clinical trials begin in human subjects.

Clinical trials are conducted in phases, each having a different purpose, and each answering different questions.  In Phase I clinical trials, the investigational new drug (IND) or treatment undergoes first-time testing in human subjects.  The subject population consists of 20-80 healthy human subjects or patients in which the drug is intended for use. The pharmacokinetic and pharmacodynamic parameters in humans, mechanism of action, safety, safe dosing range, and side effects are determined in Phase I clinical trials.  Early evidence of efficacy may also be detected, which provides data for which Phase II clinical trials are planned.

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Phase II clinical trials are conducted in a population of 100-300 human subjects.  These clinical trials are designed to evaluate the efficacy and the safety of the IND in the patient population in which it will be marketed for use.  Phase III clinical trials are larger studies, conducted in 1,000-3,000 patients suffering from the disease state in which the investigational new drug will eventually be used, that confirm the effectiveness, monitor side effects, and collect data for the safe use of the investigational new drug.  In addition, Phase III clinical trials may be designed to compare the IND to current standards of care and often provide the evidence that propels changes to clinical guidelines of diseases used by doctors.

After Phase III clinical trials have been completed and the data has been evaluated, a drug may receive approval for marketing and sale to the general population.  If the drug receives approval and is subsequently used in the general population, post-marketing data, in the form of events that are reported by patients, physicians, and by the drug company to the FDA, is collected.  Occasionally, the FDA may require Phase IV studies or clinical trials.  Circumstances that would require further evaluation of a drug in Phase IV studies or clinical trials are:  drugs that are approved under the accelerated approval process; pediatric studies that are required under the Pediatric Research Equity Act; in order to demonstrate the safety and efficacy in humans of drugs originally approved for use in animals; and to assess known or suspected serious risks associated with the use of a drug.  Post-marketing data and Phase IV studies and clinical trials are collected to further define the risks, benefits, and the optimal use of the drug in the population in which the drug is indicated.

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Adams, Christopher & Brantner, Van. “Estimating The Cost of New Drug Development: Is It Really $802 Million?”. Health Affairs March-April 2006: 420-428.

“Glossary of Clinical Trials Terms”. Clinical May 27, 2009

“Postmarket Study and Clinical Trial: Requirements and Commitments”. FDA. May 27, 200

“The New Drug Development Process: Steps from Test Tube to New Drug Application Review”. FDA. May 20, 2009

“The Beginnings: Laboratory and Animal Studies”. U.S. Food and Drug Administration. May 26, 2009

“Understanding Clinical Trials”. Clinical May 10, 2009