U.S. Food and Drug Administration
`
`Drug Approval Process
`
`What is a drug as defined by the FDA?
`A drug is any product that is intended for use in the diagnosis, cure mitigation, treatment , or
`prevention of disease; and that tis intended to affect the structure or any function of the body.
`
`Drug Sponsor’s Discovery and Screening Phase
`
`Drug Sponsor’s Clinical Studies/Trials
`
`20 80
`-
`
`The typical number of healthy volunteers used in Phase 1; this phase
`emphasizes safety. The goal here in this phase is to determine what the
`drug's most frequent side effects are and, often, how the drug is
`metabolized and excreted.
`
`100’s
`
`The typical number of patients used in Phase 2; this phase emphasizes
`effectiveness. This goal is to obtain preliminary data on whether the drug works
`in people who have a certain disease or condition. For controlled trials, patients
`receiving the drug are compared with similar patients receiving a different
`treatment--usually a placebo, or a different drug. Safety continues to be
`evaluated, and short-term side effects are studied.
`
`PHASE 1
`
`PHASE 2
`
`3 4
`
`At the end of Phase 2, FDA and sponsors discuss how large-scale studies in Phase 3 will be done.
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`Page 1
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`1000’s
`
`The typical number of patients used in Phase 3. These studies gather more
`information about safety and effectiveness, study different populations and
`different dosages, and uses the drug in combination with other drugs.
`
`PHASE 3
`
`DRUG
`SPONSOR
`
`5
`
`2
`
`1
`
`IND Application
`
`The sponsor submits an
`Investigational New Drug
`(IND) application to FDA
`based on the results from
`intial testing that include,
`the drug’s composition and
`manufacturing, and
`develops a plan for testing
`the drug on humans.
`
`Drug Developed
`
`Drug sponsor develops a
`new drug compound and
`seeks to have it approved
`by FDA for sale in the
`United States.
`
`IND REVIEW
`
`FDA reviews the IND to assure
`that the proposed studies,
`generally referred to as clinical
`trials, do not place human
`subjects at unreasonable risk of
`harm. FDA also verifies that
`there are adequate informed
`consent and human subject
`protection.
`
`Animals Tested
`
`Sponsor must test new
`drug on animals for
`toxicity. Multiple species
`are used to gather basic
`information on the safety
`and efficacy of the
`compound being
`investigated/researched.
`
`FDA’s Center for Drug
`Evaluation and Research
`(CDER) evaluates new drugs
`before they can be sold.
`
`V A LUATIO
`N A
`
`N
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`D R ESEARC
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`H
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`RU G E
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`TER FOR D
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`CEN
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`The center’s evaluation not only prevents quackery, but also
`provides doctors and patients the information they need to
`use medicines wisely. CDER ensures that drugs, both
`brand-name and generic, are effective and their health
`benefits outweigh their known risks.
`
`Boehringer Ex. 2021
`Mylan v. Boehringer Ingelheim
`IPR2016-01563
`Page 1
`
`

`
`Who reviews new drug submissions?
`A team of CDER physicians, statisticians, chemists, pharmacologists, and other
`scientists review the drug sponsor’s data and proposed labeling of drugs.
`
`What other drug products are regulated by FDA?
`Drugs include more than just medicines. For example,
`fluoride toothpastes, antiperspirants (not deodorant),
`dandruff shampoos, and sunscreens are all considered drugs.
`
`FDA’s New Drug Application (NDA)Review
`
`FDA’s Post-Approval Risk Assessment Systems
`
`Because it's not possible to predict all of a drug's effects during clinical
`trials, monitoring safety issues after drugs get on the market is critical. The
`role of FDA’s post-marketing safety system is to detect serious unexpected
`adverse events and take definitive action when needed.
`
`www.fda.gov/medwatch
`(800) FDA-1088 (322-1088) phone
`(800) FDA-0178 (322-0178) fax
`
`Once FDA approves a drug, the
`post-marketing monitoring stage begins.
`The sponsor (typically the manufacturer)
`is required to submit periodic safety
`updates to FDA.
`
`FDA’s MedWatch voluntary system makes it
`easier for physicians and consumers to report
`adverse events. Usually, when important new
`risks are uncovered, the risks are added to the
`drug's labeling and the public is informed of
`the new information through letters, public
`health advisories, and other education. In
`some cases, the use of the drug must be
`substantially limited. And in rare cases, the
`drug needs to be withdrawn from the market.
`
`Since the PDUFA was passed in 1992, more
`than 1,000 drugs and biologics have come to
`the market, including new medicines to treat
`cancer, AIDS, cardiovascular disease, and
`life-threatening infections.
`
`PDUFA has enabled the Food and Drug Administration to bring access to new drugs as fast or faster
`than anywhere in the world, all while maintaining the same thorough review process. Under PDUFA,
`drug companies agree to pay fees that boost FDA resources, and FDA agrees to time frames for its
`review of new drug applications.
`
`Page 2
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`PHASE 4
`
`FASTER APPROVALS
`
`The Accelerated Approval program allows
`earlier approval of drugs that treat serious
`diseases and that fill an unmet medical
`need. The approval is faster because FDA
`can base the drug’s effectiveness on a
`“surrogate endpoint,” such as a blood test
`or X-ray result, rather than waiting for
`results from a clinical trial.
`
`The Fast Track program helps reduce the
`time for FDA’s review of products that treat
`serious or life-threatening diseases and
`those that have the potential to address an
`unmet medical need. Drug sponsors can
`submit portions of an application as the
`information becomes available (“rolling
`submission”) instead of having to wait
`until all information is available.
`
`Facility Inspection
`
`FDA inspects the facilities where
`the drug will be manufactured.
`
`12
`
`Drug Approval
`
`FDA reviewers will approve
`the application or issue a
`response letter.
`
`Drug Labeling
`
`10
`
`FDA reviews the drug’s professional labeling
`and assures appropriate information is
`communicated to health care professionals
`and consumers.
`
`11
`
`8-9
`
`60DAY
`
`Application Reviewed
`
`After an NDA is received, FDA has 60
`days to decide whether to file it so it can
`be reviewed. If FDA files the NDA, the
`FDA Review team is assigned to evaluate
`the sponsor’s research on the drug’s
`safety and effectiveness.
`
`NDA Application
`
`The drug sponsor formally asks FDA to approve
`a drug for marketing in the United States by
`submitting an NDA. An NDA includes all animal
`and human data and analyses of the data, as
`well as information about how the drug
`behaves in the body and how it is
`manufactured.
`
`Review Meeting
`
`FDA meets with a drug sponsor prior to
`submission of a New Drug Application.
`
`67
`
`DRUG
`SPONSOR
`
`Boehringer Ex. 2021
`Mylan v. Boehringer Ingelheim
`IPR2016-01563
`Page 2