`
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`
`Guidance for Industry
`Expedited Programs for Serious
`Conditions – Drugs and
`Biologics
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`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research (CDER)
`Center for Biologics Evaluation and Research (CBER)
`
`May 2014
`Procedural
`
`OMB Control No. 0910-0765
`Expiration Date: 05/31/2020 (Note: Expiration date updated 09/21/2017)
`See additional PRA statement in section X of this guidance.
`
`
`ALKERMES EXHIBIT 2046
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Limited
`IPR2018-00943
`
`Page 1 of 40
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`

`

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`
`
`
`Guidance for Industry
`Expedited Programs for Serious
`Conditions – Drugs and
`Biologics
`
`
`
`
`Additional copies are available from:
`Office of Communications
`Division of Drug Information, WO51, Room 2201
`Center for Drug Evaluation and Research
`Food and Drug Administration
`10903 New Hampshire Ave., Silver Spring, MD 20993
`Phone: 301-796-3400; Fax: 301-847-8714
`druginfo@fda.hhs.gov
`http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
`
`and/or
`
`Office of Communication, Outreach and Development
`Center for Biologics Evaluation and Research
`Food and Drug Administration
`10903 New Hampshire Ave., WO71, Room 3128
`Silver Spring, MD 20993
`Phone: 800-835-4709 or 240-402-7800
`ocod@fda.hhs.gov
`http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
`
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research (CDER)
`Center for Biologics Evaluation and Research (CBER)
`
`
`May 2014
`Procedural
`
`Page 2 of 40
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`Contains Nonbinding Recommendations
`
`TABLE OF CONTENTS
`
`
`
`I. 
`INTRODUCTION............................................................................................................. 1 
`BACKGROUND ............................................................................................................... 1 
`II. 
`III.  CONCEPTS FOR EXPEDITED PROGRAMS ............................................................. 2 
`A.  Serious Condition ........................................................................................................................... 2 
`B.  Available Therapy .......................................................................................................................... 3 
`C.  Unmet Medical Need...................................................................................................................... 4 
`IV.  OVERVIEW OF EXPEDITED PROGRAMS ............................................................... 7 
`V. 
`FAST TRACK DESIGNATION ..................................................................................... 9 
`A.  Qualifying Criteria for Fast Track Designation .......................................................................... 9 
`B.  Features of Fast Track Designation ............................................................................................. 9 
`VI. 
`BREAKTHROUGH THERAPY DESIGNATION ..................................................... 10 
`A.  Qualifying Criteria for Breakthrough Therapy Designation................................................... 10 
`B.  Features of Breakthrough Therapy Designation ...................................................................... 13 
`VII.  ACCELERATED APPROVAL ..................................................................................... 15 
`A.  Qualifying Criteria for Accelerated Approval .......................................................................... 16 
`B.  Accelerated Approval Endpoints ................................................................................................ 17 
`C.  Evidentiary Criteria for Accelerated Approval ........................................................................ 19 
`D.  Conditions of Accelerated Approval .......................................................................................... 22 
`VIII.  PRIORITY REVIEW DESIGNATION ....................................................................... 24 
`A.  Qualifying Criteria for Priority Review Designation ............................................................... 24 
`B.  Features of Priority Review Designation ................................................................................... 25 
`IX.  GENERAL CONSIDERATIONS ................................................................................. 25 
`A.  Manufacturing and Product Quality Considerations ............................................................... 25 
`B.  Nonclinical Considerations ......................................................................................................... 26 
`C.  Clinical Inspection Considerations ............................................................................................. 27 
`D.  Companion Diagnostics ............................................................................................................... 27 
`X. 
`PAPERWORK REDUCTION ACT OF 1995 .............................................................. 27 
`APPENDIX 1: PROCESSES FOR FAST TRACK, BREAKTHROUGH THERAPY, AND
`PRIORITY REVIEW DESIGNATIONS ................................................................................. 28 
`A.  Process for Fast Track Designation ............................................................................................ 28 
`B.  Process for Breakthrough Therapy Designation ....................................................................... 30 
`
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`Contains Nonbinding Recommendations
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`C.  Process for Priority Review Designation ................................................................................... 33 
`APPENDIX 2: PROCESSES FOR ROLLING REVIEW ...................................................... 35 
`A.  Agreement on Proposal ............................................................................................................... 35 
`B.  Portions of an Application Eligible for Early Submission ....................................................... 35 
`C.  Submission of User Fees .............................................................................................................. 36 
`D.  Commencement of Review .......................................................................................................... 36 
`E.  Calculation of Review Time ........................................................................................................ 36 
`
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`ii
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`Contains Nonbinding Recommendations
`
`Guidance for Industry1
`Expedited Programs for Serious Conditions – Drugs and Biologics
`
`INTRODUCTION
`
`
`
`This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It
`does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
`You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
`and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
`implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
`number listed on the title page of this guidance.
`
`
`I.
`
`The following four FDA programs are intended to facilitate and expedite development and
`review of new drugs2 to address unmet medical need in the treatment of a serious or life-
`threatening3 condition: fast track designation, breakthrough therapy designation, accelerated
`approval, and priority review designation (see section IV for an overview of the programs). The
`purpose of this guidance for industry is to provide a single resource for information on FDA’s
`policies and procedures for these four programs as well as threshold criteria generally applicable
`to concluding that a drug is a candidate for these expedited development and review programs.
`
`FDA’s guidance documents, including this guidance, do not establish legally enforceable
`responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should
`be viewed only as recommendations, unless specific regulatory or statutory requirements are
`cited. The use of the word should in Agency guidances means that something is suggested or
`recommended, but not required.
`
`II.
`
`The programs described in this guidance are intended to help ensure that therapies for serious
`conditions are approved and available to patients as soon as it can be concluded that the
`therapies’ benefits justify their risks. The Agency first formally articulated its thinking on
`expediting the availability of promising new therapies in regulations codified at part 312, subpart
`E ( 21 CFR part 312).4 The subpart E regulations are intended to speed the availability of new
`therapies to patients with serious conditions, especially when there are no satisfactory alternative
`therapies, while preserving appropriate standards for safety and effectiveness. The regulations
`
`1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) in cooperation with the
`Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration.
`2 For the purposes of this guidance, all references to drugs or drug products include both human drugs and
`biological drug products regulated by CDER and CBER unless otherwise specified.
`3 1.
`Whether a Condition Is Serious explains that all references to serious conditions include life-threatening
`conditions.
`4 Food and Drug Administration, Interim Rule, Investigational New Drug, Antibiotic, and Biological Drug Product
`Regulations; Procedures for Drugs Intended to Treat Life-Threatening and Severely Debilitating Illnesses (53 FR
`41516, October 21, 1988).
`
`
`
`
`BACKGROUND
`
`1
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`Contains Nonbinding Recommendations
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`call for earlier attention to drugs that have promise in treating such conditions, including early
`consultation with FDA for sponsors of such products and efficient trial design, potentially
`relying on well-controlled phase 2 studies for evidence of effectiveness. The subpart E
`regulations specifically recognize that patients and physicians are generally willing to accept
`greater risks and side effects from treatment of life-threatening and severely debilitating diseases
`than they would for other diseases. The four principal programs that support these principles are
`fast track designation, breakthrough therapy designation, accelerated approval, and priority
`review designation (referred to in this guidance as the Agency’s expedited programs).
`
`FDA has a history of applying the philosophy underlying subpart E to drugs for rare diseases
`through use of the Agency’s expedited programs. FDA recognizes that certain aspects of drug
`development that are feasible for common diseases may not be feasible for rare diseases and that
`development challenges are often greater with increasing rarity of the disease. FDA will
`continue to apply flexibility in these situations to address particular challenges posed by each
`disease.
`
`III. CONCEPTS FOR EXPEDITED PROGRAMS
`
`The programs that are the subject of this guidance, fast track designation, breakthrough therapy
`designation, accelerated approval, and priority review, are summarized in section IV and
`described individually in detail in sections V, VI, VII, and VIII. All four expedited programs
`represent efforts to address an unmet medical need in the treatment of a serious condition, which
`is discussed in the following paragraphs.
`
`
`A.
`
`Serious Condition
`
`
`
`1.
`
`Whether a Condition Is Serious
`
`
`FDA intends to interpret the term serious as it has done in the past for the purposes of
`accelerated approval5 and expanded access to investigational drugs for treatment use.6 A serious
`disease or condition is defined in the expanded access regulations as follows:
`
`
`. . . a disease or condition associated with morbidity that has
`substantial impact on day-to-day functioning. Short-lived and self-
`limiting morbidity will usually not be sufficient, but the morbidity
`need not be irreversible if it is persistent or recurrent. Whether a
`disease or condition is serious is a matter of clinical judgment,
`based on its impact on such factors as survival, day-to-day
`functioning, or the likelihood that the disease, if left untreated, will
`progress from a less severe condition to a more serious one.7
`
`
`
`5 Food and Drug Administration, Final Rule, New Drug, Antibiotic, and Biological Drug Product Regulations;
`Accelerated Approval (57 FR 58942, December 11, 1992) and Food and Drug Administration, Proposed Rule, New
`Drug, Antibiotic, and Biological Drug Product Regulations; Accelerated Approval (57 FR 13234, April 15, 1992).
`6 Part 312, subpart I.
`7 21 CFR 312.300(b)(1).
`
`
`
`
`2
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`Note: For the purposes of this guidance, the terms condition, disease, and illness are used
`interchangeably. All conditions meeting the definition of life-threatening as set forth at
`§ 312.81(a) would also be serious conditions.
`
`2.
`
`Whether the Drug Is Intended to Treat a Serious Condition
`
`
`As referenced in section IV, the statutory and regulatory eligibility criteria for expedited
`programs require that a drug be intended to treat a serious condition. To satisfy this criterion, a
`drug must be intended to have an effect on a serious condition or a serious aspect of a condition,
`such as a direct effect on a serious manifestation or symptom of a condition or other intended
`effects, including the following:
`
`
`
`
`
`
` 
`
` A diagnostic product intended to improve diagnosis or detection of a serious condition in
`a way that would lead to improved outcomes
`
` 
`
` A product intended to mitigate or prevent a serious treatment-related side effect (e.g.,
`serious infections in patients receiving immunosuppressive therapy)
`
` 
`
` A product intended to avoid or diminish a serious adverse event associated with available
`therapy for a serious condition (e.g., product that is less cardiotoxic than available cancer
`therapy)8
`
` A product intended to prevent a serious condition or reduce the likelihood that the
`condition will progress to a more serious condition or a more advanced stage of disease
`
`B. Available Therapy
`
`
`For purposes of this guidance, FDA generally considers available therapy (and the terms existing
`treatment and existing therapy) as a therapy that:
`
`
`
`
`Is approved or licensed in the United States for the same indication being considered for
`the new drug9 and
`
` 
`
`Is relevant to current U.S. standard of care (SOC) for the indication
`
`
`8 Sponsors considering an expedited drug development designation or program for a drug intended to avoid a serious
`adverse event associated with available therapy or diminish its severity should be aware that they will need to
`provide data that directly support the effect corresponding to the level of evidence needed to meet the qualifying
`criteria for the relevant designation or program (e.g., phase 3 data demonstrating lower incidence or severity of the
`serious adverse reaction compared to available therapy for priority review). The requisite data may be very difficult
`to obtain in early development, particularly for purposes of breakthrough therapy designation.
`9 There may be a substantial number of approved therapies with varying relevance to how a serious disease is
`currently treated in the United States, including therapies that are no longer used or are used rarely. Only in
`exceptional cases will a treatment that is not approved for the indicated use or is not FDA-regulated (e.g., surgery)
`be considered available therapy. In those cases, FDA may consider an unapproved or unlicensed therapy to
`constitute available therapy if the safety and effectiveness of the use is supported by compelling evidence, including
`extensive evidence in the published literature (e.g., certain well-established oncologic treatments).
`3
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`
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`FDA’s available therapy determination generally focuses on treatment options that reflect the
`current SOC for the specific indication (including the disease stage) for which a product is being
`developed. In evaluating the current SOC, FDA considers recommendations by authoritative
`scientific bodies (e.g., National Comprehensive Cancer Network, American Academy of
`Neurology) based on clinical evidence and other reliable information that reflects current clinical
`practice. When a drug development program targets a subset of a broader disease population
`(e.g., a subset identified by a genetic mutation), the SOC for the broader population, if there is
`one, generally is considered available therapy for the subset, unless there is evidence that the
`SOC is less effective in the subset.
`
`Over the course of new drug development, it is foreseeable that the SOC for a given condition
`may evolve (e.g., because of approval of a new therapy or new information about available
`therapies). FDA will determine what constitutes available therapy at the time of the relevant
`regulatory decision for each expedited program a sponsor intends to use (e.g., generally early in
`development for fast track and breakthrough therapy designations, at time of biologics license
`application (BLA) or new drug application (NDA) submissions for priority review designation,
`during BLA or NDA review for accelerated approval). FDA encourages sponsors to discuss
`available therapy considerations with the Agency during interactions with FDA.
`
`As appropriate, FDA may consult with special Government employees or other experts when
`making an available therapy determination.
`
`When determining whether a drug granted accelerated approval or approved with a risk
`evaluation and mitigation strategy (REMS) that includes elements to assure safe use (ETASU)
`under section 505-1 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355-
`1), is considered available therapy, the following principles will be applied:
`
`
` A drug would not be considered available therapy if the drug is granted accelerated
`approval based on a surrogate endpoint or an intermediate clinical endpoint and clinical
`benefit has not been verified by postapproval studies. (See section III.C.3.)
`
` A drug would be considered available therapy if the drug is granted accelerated approval
`because of restricted distribution and the study population for the new drug under
`development is eligible to receive the approved drug under the restricted distribution
`program. Similarly, a drug would be considered available therapy if the study population
`for the new drug under development is eligible to receive the approved drug under the
`ETASU REMS.
`
`
`
`
`
`C.
`
`Unmet Medical Need
`
`
`An unmet medical need is a condition whose treatment or diagnosis is not addressed
`adequately by available therapy. An unmet medical need includes an immediate need
`for a defined population (i.e., to treat a serious condition with no or limited treatment) or
`a longer-term need for society (e.g., to address the development of resistance to
`antibacterial drugs).
`
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` Has an effect on a serious outcome of the condition in patients who are unable to tolerate
`or failed to respond to available therapy
`
` Can be used effectively with other critical agents that cannot be combined with available
`therapy
`
` 
`
` Provides efficacy comparable to those of available therapy, while (1) avoiding serious
`toxicity that occurs with available therapy, (2) avoiding less serious toxicity that is
`common and causes discontinuation of treatment of a serious condition, or (3) reducing
`the potential for harmful drug interactions
`
` Provides safety and efficacy comparable to those of available therapy but has a
`documented benefit, such as improved compliance, that is expected to lead to an
`improvement in serious outcomes
`
` 
`
` Addresses an emerging or anticipated public health need, such as a drug shortage
`
`In some disease settings, a drug that is not shown to provide a direct efficacy or safety advantage
`over available therapy may nonetheless provide an advantage that would be of sufficient public
`health benefit to qualify as meeting an unmet medical need. For example, in a condition for
`which there are approved therapies that have a modest response rate or significant heterogeneity
`in response, a drug with a novel mechanism of action (but comparable safety and effectiveness)
`could have the potential to provide an advantage over available therapy in some patients. In such
`a case, the novel mechanism of action should have a well-understood relationship to the disease
`pathophysiology. In addition, there should be a reasonable basis for concluding that a significant
`number of patients may respond differently to the new drug compared with available therapy.
`Thus, mechanistic diversity, even without a documented efficacy or safety advantage, could be
`5
`
`
`
`
`Where There Is No Available Therapy
`
`1.
`
`If there is no available therapy for a serious condition, there is clearly an unmet medical need.
`
`2.
`
`When available therapy exists for a condition, a new treatment generally would be considered to
`address an unmet medical need if the treatment:
`
`
`Where There Is Available Therapy
`
` Has an effect on a serious outcome of the condition that is not known to be influenced by
`available therapy (e.g., progressive disability or disease progression when the available
`therapy has shown an effect on symptoms, but has not shown an effect on progressive
`disability or disease progression)
`
` Has an improved effect on a serious outcome(s) of the condition compared with available
`therapy (e.g., superiority of the new drug to available therapy when either used alone or
`in combination with available therapy (i.e., as demonstrated in an add-on study))
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`Contains Nonbinding Recommendations
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`advantageous in disease settings in which drugs become less effective or ineffective over time.
`For example, infectious disease drugs or targeted cancer therapies with novel mechanisms of
`action, although appearing to have efficacy similar to available therapy across the disease
`population, could benefit patients who no longer respond to available therapy. Accordingly,
`FDA intends to consider a range of potential advantages over available therapy beyond those
`shown in head-to-head comparisons.
`
`
`3.
`
`Where the Only Available Therapy Was Approved Under the Accelerated
`Approval Program Based on a Surrogate Endpoint or an Intermediate Clinical
`Endpoint and Clinical Benefit Has Not Yet Been Verified
`
`
`As discussed in sections VII and III.B., FDA recognizes, as a general matter, that it is preferable
`to have more than one treatment approved under the accelerated approval provisions because of
`the possibility that clinical benefit may not be verified in postapproval confirmatory trials. FDA
`will therefore consider products as addressing an unmet medical need if the only approved
`treatments were granted accelerated approval based on a surrogate endpoint or an intermediate
`clinical endpoint and clinical benefit has not been verified by postapproval studies.
`
`
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`Contains Nonbinding Recommendations
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`IV. OVERVIEW OF EXPEDITED PROGRAMS
`
`The table provides an overview of the four expedited programs. Additional details on the specific
`programs are found in the sections that follow. Note that a drug development program may qualify
`for more than one expedited program.
`
`Comparison of FDA’s Expedited Programs for Serious Conditions
`
`Fast Track
`Breakthrough
`Therapy
`Designation
`
`Designation
`
`Approval Pathway
`
`Designation
`
`Accelerated Approval
`
`Priority Review
`
`Nature of
`program
`Reference
`
`Qualifying
`criteria
`
` Section 506(b) of the
`FD&C Act, as added
`by section 112 of the
`Food and Drug
`Administration
`Modernization Act of
`1997 (FDAMA) and
`amended by section
`901 of the Food and
`Drug Administration
`Safety and Innovation
`Act of 2012
`(FDASIA)
` A drug that is
`intended to treat a
`serious condition
`AND nonclinical or
`clinical data
`demonstrate the
`potential to address
`unmet medical need
`OR
` A drug that has been
`designated as a
`qualified infectious
`disease producta
`
`
` Section 506(a) of the
`FD&C Act, as added
`by section 902 of
`FDASIA
`
` 21 CFR part 314, subpart H
` 21 CFR part 601, subpart E
` Section 506(c) of the FD&C
`Act, as amended by section
`901 of FDASIA
`
` Prescription Drug
`User Fee Act of
`1992
`
`
`
` A drug that is
`intended to treat a
`serious condition
`AND preliminary
`clinical evidence
`indicates that the drug
`may demonstrate
`substantial
`improvement on a
`clinically significant
`endpoint(s) over
`available therapies
`
`
` A drug that treats a serious
`condition AND generally
`provides a meaningful
`advantage over available
`therapies AND
`demonstrates an effect on a
`surrogate endpoint that is
`reasonably likely to predict
`clinical benefit or on a
`clinical endpoint that can be
`measured earlier than
`irreversible morbidity or
`mortality (IMM) that is
`reasonably likely to predict
`an effect on IMM or other
`clinical benefit (i.e., an
`intermediate clinical
`endpoint)
`
` An application
`(original or
`efficacy
`supplement) for a
`drug that treats a
`serious condition
`AND, if
`approved, would
`provide a
`significant
`improvement in
`safety or
`effectiveness OR
` Any supplement
`that proposes a
`labeling change
`pursuant to a
`report on a
`pediatric study
`under 505Ab OR
` An application for
`a drug that has
`been designated
`as a qualified
`infectious disease
`productc OR
` Any application
`or supplement for
`a drug submitted
`with a priority
`review voucherd
`
`
`
`
`
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`Contains Nonbinding Recommendations
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`Comparison of FDA’s Expedited Programs for Serious Conditions
`
`Fast Track
`Breakthrough
`Therapy
`Designation
`
`Nature of
`program
`When to
`submit request
`
`Designation
`
` With IND or after
` Ideally, no later than
`the pre-BLA or pre-
`NDA meeting
`
` With IND or after
` Ideally, no later than
`the end-of-phase 2
`meeting
`
`Timelines for
`FDA response
`
` Within 60 calendar
`days of receipt of the
`request
`
` Within 60 calendar
`days of receipt of the
`request
`
`Features
`
` Actions to expedite
`development and
`review
` Rolling review
`
`
`Additional
`considerations
`
` Designation may be
`rescinded if it no
`longer meets the
`qualifying criteria for
`fast trackf
`
` Intensive guidance on
`efficient drug
`development
` Organizational
`commitment
` Rolling review
` Other actions to
`expedite review
` Designation may be
`rescinded if it no
`longer meets the
`qualifying criteria for
`breakthrough therapyg
`
`
`
`
`
`8
`
`Accelerated Approval
`
`Approval Pathway
`
` The sponsor should
`ordinarily discuss the
`possibility of accelerated
`approval with the review
`division during
`development, supporting,
`for example, the use of the
`planned endpoint as a basis
`for approval and discussing
`the confirmatory trials,
`which should usually be
`already underway at the
`time of approval
` Not specified
`
` Approval based on an effect
`on a surrogate endpoint or
`an intermediate clinical
`endpoint that is reasonably
`likely to predict a drug’s
`clinical benefit
`
`Priority Review
`
`Designation
`
` With original
`BLA, NDA, or
`efficacy
`supplement
`
` Within 60
`calendar days of
`receipt of original
`BLA, NDA, or
`efficacy
`supplement
` Shorter clock for
`review of
`marketing
`application (6
`months compared
`with the 10-month
`standard review)e
`
` Designation will
`be assigned at the
`time of original
`BLA, NDA, or
`efficacy
`supplement filing
`
` Promotional materials
` Confirmatory trials to verify
`and describe the anticipated
`effect on IMM or other
`clinical benefit
` Subject to expedited
`withdrawal
`a Title VIII of FDASIA, Generating Antibiotic Incentives Now (GAIN), provides incentives for the development of antibacterial and
`antifungal drugs for human use intended to treat serious and life threatening infections. Under GAIN, a drug may be designated as a
`qualified infectious disease product (QIDP) if it meets the criteria outlined in the statute. A drug that receives QIDP designation is eligible
`under the statute for fast track designation and priority review. However, QIDP designation is beyond the scope of this guidance.
`b Any supplement to an application under section 505 of the FD&C Act that proposes a labeling change pursuant to a report on a pediatric
`study under this section shall be considered a priority review supplement per section 505A of the FD&C Act as amended by section 5(b) of
`the Best Pharmaceuticals for Children Act.
`c See footnote a above.
`d Any application or supplement that is submitted with a priority review voucher will be assigned a priority review. Priority review
`vouchers will be granted to applicants of applications for drugs for the treatment or prevention of certain tropical diseases, as defined in
`section 524(a)(3) and (a)(4) of the FD&C Act and for treatment of rare pediatric diseases as defined in section 529(a)(3) of the FD&C Act.
`e As part of its commitments in PDUFA V, FDA has established a review model, the Program. The Program applies to all new molecular
`entity NDAs and original BLAs, including applications that are resubmitted following a Refuse-to-File action, received from October 1,
`2012, through September 30, 2017. For applications filed by FDA under the Program, the PDUFA review clock will begin at the
`conclusion of the 60 calendar day filing review period that begins on the date of FDA receipt of the original submission.
`f A sponsor may also withdraw fast track designation if the designation is no longer supported by emerging data or the drug development
`program is no longer being pursued (see section A.5. of Appendix 1).
`g A sponsor may also withdraw breakthrough therapy designation if the designation is no longer supported by emerging data or the drug
`development program is no longer being pursued (see section B.5. of Appendix 1).
`
`Page 12 of 40
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`Contains Nonbinding Recommendations
`
`FAST TRACK DESIGNATION
`
`
`V.
`
`Section 506(b) of the FD&C Act provides for the designation of a drug as a fast track product
`“. . . if it is intended, whether alone or in combination with one or more other drugs, for the
`treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to
`address unmet medical needs for such a disease or condition.” This provision is intended to
`facilitate development and expedite review of drugs to treat serious and life-threatening
`conditions so that an approved product can reach the market expeditiously. This section
`describes the qualifying criteria and the features of fast track designation. Appendix 1 describes
`the process for fast track designation.
`
`
`A.
`
`Qualifying Criteria for Fast Track Designation
`
`
`Fast track designation applies to the drug (either alone or in combination with other drugs) and
`the specific use for which it is being studied. The term drug refers to the combination of two or
`more drugs if the combination is the subject of the fast track designation or request. Where
`appropriate, FDA may grant designation to the development of a new use of an approved drug.
`
`
`Serious Condition
`
`1.
`
`See section III.A.
`
`
`Demonstrating the Potential to Address Unmet Medical Need
`
`2.
`
`The type of information needed to demonstrate the potential of a drug to address an unmet
`medical need will depend on the stage of drug development at which fast track designation is
`requested. Early in development, evidence of activity in a nonclinical model, a mechanistic
`rationale, or pharmacologic data could be used to demonstrate such potential. Later in
`development, available clinical data should demonstrate the potential to address an unmet
`medical need. See section III.C.
`
`
`B.
`
`Features of Fast Track Designation
`
`
`
`1.
`
`Actions to Expedite Development and Review
`
`
`There are opportunities for frequent interactions with the review team for a fast track product.
`These include meetings with FDA, including pre-IND meetings, end-