3/16/2017
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`The Drug Development and Approval Process: FDAReview.org
`
`FDAReview.org
`
`a project of the Independent Institute
`
`The Drug Development and Approval Process
`
`Drug Development
`
`The Drug Development and Approval Process
`
`The process of getting a drug to market, from first testing to final FDA approval, is summarized in figure
`1 and described at greater length below.
`
`Figure 1
`
`An Overview of the Drug Development Process
`
`Toxicology
`
`Investigational
`New Drug
`Application
`
`Clinical
`Phase I
`
`Phase II
`
`Phase III
`
`Approval
`New Drug
`Application
`
`Phase IV /
`Postmarket
`surveillance
`
`Expenses
`
`Time
`
`safety
`
`$15.2
`million
`
`21.6
`months
`
`safety
`dosing
`efficacy
`
`$23 .4
`million
`
`25.7
`months
`
`safety
`efficacy
`side effects
`
`$86.5
`million
`
`30.5 months
`
`I to 6 years
`
`6 to 11 years
`
`0.6 to 2
`years
`
`II to l4 years
`
`Overall probability of success
`
`‘2
`Conditional probability of success
`
`22
`Sources: Dimasi, Hansen, and Grabowski (2003).
`
`Notes: The line marked “Overall probability of success” is the unconditional probability of reaching a
`given stage. For example, 30 percent of drugs make it to phase I testing. The line marked
`“Conditional probability of success” shows the probability of advancing to the next stage of the
`process conditional on reaching a given stage. For example, the probability of advancing to Phase III
`testing conditional on starting Phase II testing is 48 percent.
`
`Drug companies continuously analyze thousands of compounds, seeking ones of therapeutic value.
`During the six to seven years of preclinical testing, the manufacturer completes synthesis and
`purification of the drug and conducts limited animal testing. Of five thousand compounds tested,
`approximately five will appear promising enough to induce the company to file an Investigational New
`Drug Application (IND). If the IND is approved by the FDA and by an Institutional Review Board, the
`manufacturer may begin the first phase of development.
`
`The IND stage consists of three phases. In phase I, clinical trials using healthy individuals are conducted
`to determine the drug’s basic properties and safety profile in humans. Typically the drug remains in this
`stage for one to two years. In phase II, efficacy trials begin as the drug is administered to volunteers of
`the target population. At the end of phase II, the manufacturer meets with FDA officials to discuss the
`development process, continued human testing, any concerns the FDA may have, and the protocols for
`phase III, which is usually the most extensive and most expensive part of drug development. During the
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`http://www.fdareview.org/O3_drug_deve|opment.php
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`3/16/2017
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`The Drug Development and Approval Process: FDAReview.org
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`phases of the IND, the manufacturer can obtain accelerated development/review of the drug. Other
`accommodations for usage prior to approval include treatment IND and parallel tracking.
`
`Once phase III is complete, the manufacturer files an NDA. Review of the NDA typically lasts one to
`two years, bringing total drug development and approval (that is, the IND and NDA stages) to
`approximately nine years. During the NDA stage, the FDA consults advisory committees made of
`experts to obtain a broader range of advice on drug safety, effectiveness, and labeling. Once approved,
`the drug may be marketed with FDA regulated labeling. The FDA also gathers safety information as the
`drug is used and adverse events are reported, and it will occasionally request changes in a labeling or
`will submit press releases as new contraindications arise. If adverse events appear to be systematic and
`serious, the FDA may withdraw a product from the market.
`
`Over time there has been a clear tendency for FDA regulations and requirements to expand and multiply.
`In 1980, the typical drug underwent thirty clinical trials involving about fifteen hundred patients. By the
`mid-1990s, the typical drug had to undergo more than sixty clinical trials involving nearly five thousand
`patients.
`
`Public Agenda Online has some useful background information on medical and drug research in the
`form of easy-to-read charts.
`
`© 2016 Independent Institute
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`http://www.fdareview.org/03_drug_deve|opm ent.php
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