Guidance for Industry 

Fast Track Drug 

Development Programs —

Designation, Development, 

and Application Review 

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) 

July 2004 

Procedural 

Revision 1 
Guidance for Industry 

Fast Track Drug 

Development Programs —

Designation, Development, 

and Application Review 

Additional copies are available from: 

 

Center for Drug Evaluation and Research

Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857

(Tel) 301-827-4573

 http://www.fda.gov/cder/guidance/index.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) 

July 2004 

Procedural 

Revision 1 
TABLE OF CONTENTS 

I. INTRODUCTION................................................................................................................. 1

II. BACKGROUND ................................................................................................................... 2 

III. CRITERIA FOR QUALIFYING FOR A FAST TRACK DRUG DEVELOPMENT 

PROGRAM ................................................................................................................................... 3 

A. Serious or Life-Threatening Condition........................................................................................3

1. Whether a condition is serious.........................................................................................................4 

2. Whether the drug is intended to treat a serious condition...............................................................4 

B. Demonstrating the Potential to Address Unmet Medical Needs................................................5 

1. Evaluation of whether the drug development plan addresses unmet medical needs.......................5 

2. Demonstration of the drug's potential .............................................................................................7 

IV. PROCESS FOR DESIGNATING A DRUG FOR THE FAST TRACK DRUG 

DEVELOPMENT PROGRAM................................................................................................... 7 

A. Timing of Submission ....................................................................................................................8 

B. Where to Send a Fast Track Designation Submission................................................................8 

C. Content of a Fast Track Designation Submission.......................................................................8 

1. In general.........................................................................................................................................8 

2. Discussion and supporting documentation......................................................................................8

D. FDA Response ................................................................................................................................9 

1. Designation letter ............................................................................................................................9 

2. Non-designation letter .....................................................................................................................9 

E. Continued Designation as a Fast Track Drug Development Program......................................9 

V. PROGRAMS FOR EXPEDITING DEVELOPMENT AND REVIEW........................ 10 

A. Meetings........................................................................................................................................10 

B. Written Correspondence .............................................................................................................11 

C. Review Programs.........................................................................................................................12 

1. Priority review of BLAs and NDAs................................................................................................12 

2. Submission of portions of an application.......................................................................................12 

3. Accelerated Approval.....................................................................................................................14 

D. Dispute Resolution .......................................................................................................................15 

APPENDIX 1: SECTION 112 OF THE................................................................................... 16 

FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT OF 1997.................. 16 

APPENDIX 2: PROCEDURES FOR DRUGS INTENDED TO TREAT............................ 18 

LIFE-THREATENING AND SEVERELY DEBILITATING ILLNESSES........................ 18 

APPENDIX 3: PRIORITY REVIEW POLICIES.................................................................. 19 

APPENDIX 4: ACCELERATED APPROVAL OF NEW DRUGS AND BIOLOGICAL 

PRODUCTS FOR SERIOUS OR LIFE-THREATENING ILLNESSES............................. 20 
Contains Nonbinding Recommendations

Guidance for Industry1

Fast Track Drug Development Programs – Designation, 

Development, and Application Review 

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. 

An alternative approach may be used if such 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. INTRODUCTION 

The fast track programs of the Food and Drug Administration (FDA) are designed to facilitate 

the development and expedite the review of new drugs that are intended to treat serious or lifethreatening conditions and that demonstrate the potential to address unmet medical needs (fast 

track products). This document provides guidance to industry on the regulations, policies, and 

procedures related to the Agency's fast track programs. The guidance also clarifies the criteria 

and processes for designating fast track products. 

This guidance revises the Fast Track guidance that published September 1998. The revision is 

intended to make it clear that a drug can be said to address an unmet medical need if the only 

available treatments for the condition are approved under the accelerated approval regulations 

(21 CFR. 314.500 and 601.40), either on the basis of an effect on a surrogate endpoint or with 

restrictions on distribution. Minor editorial changes also have been made to make this guidance 

consistent with the Agency's good guidance practices (GGP) regulation (21 CFR 10.115). 

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.

1

 This guidance was developed by the Center for Drug Evaluation and Research (CDER) and the Center for Bioloics 

Evaluation and Research (CBER) in the Food and Drug Administration. 

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Contains Nonbinding Recommendations

II. BACKGROUND 

Section 112 of the Food and Drug Administration Modernization Act of 1997 (the 

Modernization Act) (P.L. 105-115) (Appendix 1) amended the Federal Food, Drug, and 

Cosmetic Act (the Act) by adding new section 506 (21 U.S.C. 356). The Modernization Act 

directed FDA to issue guidance describing its policies and procedures pertaining to fast track 

products. Section 506 authorizes FDA to take actions appropriate to facilitate the development 

and expedite the review of an application for such a product. These actions are not limited to 

those specified in the fast track provision but also encompass existing FDA programs to facilitate 

development and review of products for serious and life-threatening conditions. Such programs 

include (a) the procedures described in the 1988 interim rule "Procedures for Drugs Intended to 

Treat Life-Threatening and Severely Debilitating Illnesses" (21 CFR 312.80 through 312.88 

(Subpart E)), in which FDA formalized certain procedures to facilitate the development of 

promising therapies (Appendix 2), and (b) the priority review procedures of the Center for 

Biologics Evaluation and Research and the Center for Drug Evaluation and Research (CDER) 

(Appendix 3).2

 

Under the Subpart E regulations for investigational new drugs (Appendix 2), drug development 

is considered a continuum from early preclinical and clinical studies through submission of a 

marketing application. The regulations emphasize the critical nature of close early 

communication between the Agency and a sponsor, outline procedures such as pre-IND and end 

of phase 1 meetings as methods to improve the efficiency of preclinical and clinical 

development, and focus on efforts by the Agency and the sponsor to reach early agreement on 

the design of the major clinical efficacy studies that will be needed to support approval. 

CBER and CDER have longstanding policies that describe criteria for review priority 

classification of marketing applications. Products regulated by CBER are eligible for priority 

review if they provide a significant improvement in the safety or effectiveness of the treatment, 

diagnosis, or prevention of a serious or life-threatening disease (see Appendix 3). Products 

regulated by CDER are eligible for priority review if they provide a significant improvement 

compared to marketed products in the treatment, diagnosis, or prevention of a disease; eligibility 

is not limited to drugs for a serious or life-threatening disease (see Appendix 3). A fast track 

product would ordinarily meet either Center's criteria for priority review. Note, however, that an 

NDA or BLA sponsor need not seek fast track designation to be eligible for priority review. 

The Modernization Act specifically permits FDA to: 

1. Approve a marketing application under section 505(c) of the Act or section 351 of the 

Public Health Service Act "upon a determination that the product has an effect on a 

clinical endpoint or on a surrogate endpoint that is reasonably likely to predict clinical 

benefit." This, in effect, codifies in statute FDA's Accelerated Approval Rule (Appendix 

4), made final in 1992, which allows expedited marketing of certain new drugs or 

biological products intended to treat serious or life-threatening illnesses and that appear 

 

2

 CBER and CDER describe their priority review procedures in SOPP 8405, Complete Review and Issuance of

Action Letters (June 11, 1998) and MaPP 6020.3, Priority Review Policy (April 22, 1996), respectively. 

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Contains Nonbinding Recommendations

to provide meaningful therapeutic benefits to patients compared with existing treatments. 

Under this rule, "FDA may grant marketing approval for a new drug [or biological] 

product on the basis of adequate and well-controlled trials establishing that the drug [or 

biological] product has an effect on a surrogate endpoint that is reasonably likely, based 

on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical 

benefit or on the basis of an effect on a clinical endpoint other than survival or 

irreversible morbidity." Where an accelerated approval is based upon a surrogate 

endpoint or on an effect on a clinical endpoint other than survival or irreversible 

morbidity, postmarketing studies are ordinarily required "to verify and describe the drug's 

clinical benefit and to resolve remaining uncertainty as to the relation of the surrogate 

endpoint upon which approval was based to clinical benefit, or the observed clinical 

benefit to ultimate outcome" (57 FR 58942, December 11, 1992). 

2. Accept for review portions of a marketing application prior to receipt of the complete 

application. 

Fast track programs should be distinguished from expanded access programs for investigational 

drugs such as the treatment investigational new drug (IND) regulations (52 FR 19466, May 22, 

1987; codified as 21 CFR 312.34). Fast track 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. Expanded access programs such as the treatment IND are 

intended to facilitate access to investigational drugs prior to approval for patients with serious 

and life-threatening conditions and without therapeutic alternatives. 

III. CRITERIA FOR QUALIFYING FOR A FAST TRACK DRUG DEVELOPMENT 

PROGRAM 

Section 506(a)(1) of the Act states that a drug designated as a fast track product is intended for 

the treatment of a serious or life-threatening condition and demonstrates the potential to address 

unmet medical needs for the condition. The fast track classification thus does not apply to a 

product alone, but applies to a combination of the product and specific indication for which it is 

being studied. The indication, for the purposes of this document, includes both the condition for 

which the drug is intended (e.g., heart failure) and the anticipated or established benefits of use 

(e.g., improved exercise tolerance, decreased hospitalization, increased survival). It is therefore 

the development program for a specific drug for a specific indication that will receive fast track 

designation. Such a program is referred to in this document as a fast track drug development 

program and the criteria involved in designation are represented in Figure 1. These criteria are 

more fully described below. 

A. Serious or Life-Threatening Condition 

This section of the document provides specific guidance regarding how the Agency intends to 

determine whether a condition is serious and whether a drug is intended to treat a serious 

condition. All conditions meeting the definition of life-threatening as set forth at 21 CFR 

312.81(a) would also be serious conditions. Because the benefits of fast track designation apply 

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Contains Nonbinding Recommendations

to products for serious conditions as well as to products for life-threatening conditions, 

distinction between the two categories of conditions with regard to eligibility for fast track 

programs is unnecessary. Therefore, in the following discussion, all references to serious 

conditions will include life-threatening conditions. 

1. Whether a condition is serious 

As discussed in the preamble to the proposed accelerated approval rule (57 FR 13234, April 15, 

1992), determination of the seriousness of a condition:

... is a matter of judgment, but generally is 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. Thus, acquired 

immunodeficiency syndrome (AIDS), all other stages of human immunodeficiency

virus (HIV) infection, Alzheimer's dementia, angina pectoris, heart failure, cancer, 

and many other diseases are clearly serious in their full manifestations. Further, 

many chronic illnesses that are generally well-managed by available therapy can have 

serious outcomes [such as] ... inflammatory bowel disease, asthma, rheumatoid 

arthritis, diabetes mellitus, systemic lupus erythematosus, depression, psychoses, and 

many other diseases. 

 

For a condition to be serious, the condition should be 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, providing it is persistent or 

recurrent. 

2. Whether the drug is intended to treat a serious condition 

For a product to be in a fast track drug development program, it must not only be used in patients 

with a serious condition, it must be intended to treat a serious aspect of that condition. Thus, in 

making a fast track determination, FDA will assess whether the development program is 

designed to demonstrate an effect on a serious aspect of the condition. The following examples 

illustrate FDA's approach: 

a. A therapeutic product directed at some aspect of a serious condition would be 

considered to treat a serious condition if it were being evaluated for effects on a 

serious manifestation(s) or serious symptom(s) of the condition. 

b. A diagnostic product would be considered to treat a serious condition if it were 

being evaluated directly for its impact on a serious aspect of the condition or if it 

were being evaluated for its ability to improve diagnosis or detection of the 

condition and scientific data provided a strong basis for a presumption that the 

improvements in diagnosis or detection of the condition would lead to improved 

outcome. 

c. A preventive product would be considered to treat a serious condition if (1) it 

were being evaluated for its ability to prevent a serious manifestation(s) of the 

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Contains Nonbinding Recommendations

condition, or (2) it were being studied for its ability to prevent the condition and it 

was scientifically reasonable to assume that prevention of the condition would 

prevent its serious consequences. 

d. A product intended to ameliorate or prevent a side effect of therapy of a condition 

would be considered to treat a serious condition if the side effect were serious 

(e.g., serious infections in patients receiving immunosuppressive therapy). 

e. A product intended and being studied for its ability to treat a condition while 

avoiding the side effects of currently accepted treatments of the condition might 

be considered to treat a serious condition if such side effects were serious (e.g., a 

less myelosuppressive treatment for a tumor or an anti-inflammatory drug that 

does not cause gastrointestinal bleeding). The potential for a new drug to avoid 

the serious sequelae of existing drugs would qualify that drug development 

program for fast track designation only in limited circumstances. Many therapies, 

even those intended to treat nonserious conditions, are associated with rare, 

serious, adverse reactions, and new therapies, despite initial hopes, often are 

associated with their own set of serious reactions. Nonetheless, some adverse 

reactions are significant public health problems, and the development of therapies 

that do not cause such serious reactions would merit close attention. The Agency 

may designate the development of such a therapy as a fast track drug development 

program when (1) currently accepted therapy is widely used despite an 

unavoidable serious risk, (2) serious outcomes are a significant public health 

issue, and (3) the new therapy shows significant potential to have a substantially 

improved overall safety profile with at least similar efficacy. 

Many conditions not generally considered to be serious have rare or distant serious sequelae 

(e.g., urinary tract infections or duodenal ulcers). Product development programs for such 

conditions could be designated as fast track if the sponsor specifically designs the development 

program to demonstrate an effect on those serious sequelae. Conversely, some conditions that 

are generally considered to be serious have nonserious manifestations requiring symptomatic 

therapy (e.g., insomnia associated with schizophrenia, skin discoloration from Addison's disease, 

alopecia with lupus, subcutaneous nodules from rheumatoid arthritis). The Agency will not 

generally designate as fast track a development program for a product whose effect has been 

measured in terms of nonserious manifestations unless the product's effect on those 

manifestations is reasonably likely to predict benefit on a serious manifestation. 

B. Demonstrating the Potential to Address Unmet Medical Needs 

Section 506(a) of the Act further requires that the drug demonstrate the potential to address 

unmet medical needs. Thus, in designating a fast track drug development program, the Agency 

will determine whether the drug has a potential to address unmet medical needs and whether the 

development program is designed to evaluate this potential. 

1. Evaluation of whether the drug development plan addresses unmet medical needs 

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Contains Nonbinding Recommendations

An unmet medical need is a medical need that is not addressed adequately by an existing 

therapy. 

a. Where there is no available therapy for the condition 

If no therapy exists for a serious condition, there is an obvious unmet medical 

need and a new treatment effective in that condition would meet this aspect of the 

criteria for fast track designation. 

b. Where there is available therapy for the condition 

When therapies exist for a condition, the developmental program for the new 

agent would address unmet medical needs if it evaluated any of the following: 

i. Improved effect(s) on serious outcomes of the condition that are 

affected by alternate therapies (e.g., superiority of the new drug used 

alone or in combination with other therapies in an active controlled 

trial assessing an endpoint reflecting serious morbidity). 

ii. Effect(s) on serious outcomes of the condition not known to be 

affected by the alternatives (e.g., progressive disability in multiple 

sclerosis when the alternative treatments have shown an effect on 

exacerbations but have not shown an effect on progressive disability). 

iii. Ability to provide benefit(s) in patients who are unable to tolerate or

are unresponsive to alternative agents (e.g., an antipsychotic agent that 

is effective in people failing standard therapy), or an ability to be used 

effectively in combination with other critical agents that cannot be 

combined with available therapy. 

iv. Ability to provide benefit(s) similar to those of alternatives while 

avoiding serious toxicity that is present in existing therapies, or 

avoiding less serious toxicity that is common and causes 

discontinuation of treatment of a serious disease. 

v. Ability to provide benefit(s) similar to those of alternatives but with 

improvement in some factor, such as compliance or convenience, that 

is shown to lead to improved effects on serious outcomes. 

c. Where the only available therapy is approved under the accelerated 

approval regulations (either on the basis of an effect on a surrogate 

endpoint or for restricted distribution) 

A drug can be said to address an unmet medical need if the only available 

treatment(s) for the condition are approved under the accelerated approval 

regulations (21 CFR 314.500 and 601.40), either on the basis of an effect on a 

surrogate endpoint or with restrictions on distribution. 

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Contains Nonbinding Recommendations

FDA recognizes that, as a general matter, it is preferable to have more than one 

treatment approved under the accelerated approval provisions because of the 

uncertainty inherent in an approval under these provisions. For example, postapproval studies of a drug product may fail to establish a relationship of the 

surrogate endpoint to clinical benefit, or of the observed clinical benefit to 

ultimate outcome. In these circumstances, it is important to continue to 

expedite the development and review of important new therapies for serious and 

life-threatening illnesses under the accelerated approval provisions. Therefore, 

if the only therapies that exist for a condition are approved under the accelerated 

approval regulations on the basis of a surrogate endpoint or are approved with 

restrictions on distribution necessary to ensure the safe use of the drug, FDA 

may designate a product as fast track notwithstanding the availability of other 

therapies approved under the accelerated approval regulations. 

2. Demonstration of the drug's potential 

The type of information needed to demonstrate the potential of a drug to address unmet medical 

needs will depend on the stage of drug development. Data that become available during clinical 

development should support the drug's potential to address unmet medical needs and the 

development plan should be designed to assess this potential. The Agency will rely on 

summaries of available data to determine whether the potential to address unmet medical needs 

has been demonstrated. 

Before human studies begin, the potential for a drug to address unmet medical needs will be 

based on pharmacologic and animal model data. At this stage, there may be little evidence of 

effectiveness of the drug in humans and the potential will be largely theoretical. For later fast

track designation, but still prior to the completion of the principal controlled trials, available 

clinical data should begin to confirm or be consistent with the potential to address unmet medical 

needs. Still later in the development of a drug, the Agency will normally consider whether the 

clinical data from controlled and uncontrolled trials, as summarized by the sponsor, support the 

potential of the drug to address unmet medical needs. At this later stage in development, when 

an alternate therapy is available, the Agency's determination will also be based on whether the 

new therapy has been evaluated by comparison with the existing therapy, usually by direct 

comparison in clinical trials. As noted above, if the only existing therapy is approved under the 

accelerated approval regulations, the relevant comparisons are to conventionally approved drugs 

(i.e., drugs approved under 21 CFR 314.105, 314.125, or 601.2), or drugs approved without 

restrictions, if there are any in either category. Evidence that a new therapy was less safe than a 

drug approved under the accelerated approval regulations could, however, be relevant.

IV. PROCESS FOR DESIGNATING A DRUG FOR THE FAST TRACK DRUG 

DEVELOPMENT PROGRAM 

The general procedures applicable to the submission and review of fast track designation 

requests are described below. 

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Contains Nonbinding Recommendations

A. Timing of Submission 

A sponsor may submit a request for fast track designation at the time of original submission of 

its IND, or at any time thereafter prior to receiving marketing approval of its BLA or NDA. 

Note that the IND and potential fast track designation may be discussed prior to an IND 

submission in a pre-IND meeting, but a decision on designation would await submission of the 

IND. Although benefits associated with fast track designation may occur throughout the drug 

development process, from the early IND submission to evaluation of a marketing application, as 

a practical matter, requests should ordinarily occur no later than the sponsor's pre-BLA/NDA 

meeting with the Agency, as many of the benefits of fast track designation will no longer be 

applicable after that time. 

B. Where to Send a Fast Track Designation Submission 

A request for fast track designation should be submitted as an amendment to the sponsor's IND 

in triplicate with Form FDA 1571 attached or, if the request is simultaneous with submission of 

the original IND, should accompany the IND. The request for fast track designation should 

identify the sponsor's contact person, including the person's address, telephone number, and fax 

number. The IND or amendment should be submitted to the attention of the appropriate division 

in CBER or CDER and should clearly identify the submission as a "Request for Fast Track 

Designation." In the unusual situation where a request is made after the filing of a BLA or NDA, 

the request should be submitted to the BLA or NDA with a Form FDA 356h. 

 

C. Content of a Fast Track Designation Submission 

 1. In general 

The submission in support of a request for fast track designation should establish that the criteria 

necessary for designation are met: (1) that the drug is intended to treat a serious or life 

threatening condition (see section III.A. above), and (2) that the drug has the potential to address 

unmet medical needs and this potential is being evaluated in the planned drug development 

program (see section III.B. above). The sponsor should identify the serious condition and the 

unmet medical needs, provide a plausible basis for the assertion that the drug has the potential to 

address such unmet medical needs, and include in the development plan (at a level of detail 

appropriate to the stage of development) trials designed to evaluate this potential. 

2. Discussion and supporting documentation 

To facilitate FDA review, a submission for fast track designation should contain all discussion 

and supporting documentation necessary to permit a reviewer to assess whether the criteria for 

fast track designation are met without having to refer to information located elsewhere, yet 

should also not be voluminous. The amount of discussion and supporting documentation that 

shows that the criteria are met will vary. For example, little explanation or supporting 

documentation may be needed to establish that studying the drug in the treatment of a fatal 

condition with no approved treatment would qualify if the endpoint were mortality. More 

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Contains Nonbinding Recommendations

extensive explanation and supporting documentation would likely be submitted to show that for 

a nonfatal condition, serious or life-threatening aspects of the condition will be studied. Where 

acceptable therapy for the condition already exists, still more extensive discussion and

supporting documentation would probably be submitted to establish that the new therapy has the 

potential to fill a medical need not met by existing therapy. 

Any data or published reports that support assertions made in the discussion section of the fast 

track submission and that have not previously been submitted to the sponsor's IND should be 

included in the submission. Supporting data already contained in the sponsor's IND generally 

need only be summarized in the fast track submission with reference to its location in the IND. 

For assertions made in the submission that are consistent with accepted medical knowledge, the 

sponsor does not need to include references to clinical data or other external sources. If a 

sponsor references a large number of sources, a list of those references should be included. 

D. FDA Response 

FDA will respond to a request for fast track designation within 60 calendar days of receipt of the 

request. 

 1. Designation letter 

If the Agency determines that the criteria for designation as a fast track drug development 

program have been met, the designation letter will (1) state that fast track designation is granted 

for development of the product for use in treating the specific serious or life-threatening 

condition, (2) point out that the sponsor should design and perform studies that can show 

whether the product fulfills unmet medical needs, and (3) alert the sponsor that the drug 

development program is expected to continue to meet the criteria for fast track designation (see 

section IV.E. below). 

 2. Non-designation letter 

A nondesignation letter would reflect a determination that the request was incomplete or that the 

drug development program failed to meet the criteria for fast track designation. The 

nondesignation letter will explain the reasons for the Agency's decision. FDA will respond to a 

subsequent request for fast track designation after a nondesignation determination within 60 

calendar days of receiving the subsequent request.

E. Continued Designation as a Fast Track Drug Development Program 

It is foreseeable that, for certain products in fast track drug development programs, it will 

become apparent over the course of drug development that the development programs do not 

continue to meet the criteria for fast track designation. A product in a fast track development 

program may not continue to meet the criteria if the drug no longer (1) demonstrates a potential 

to address unmet medical needs, or (2) is being studied in a manner that would show the product 

is able to treat a serious or life-threatening condition and fulfills unmet medical needs. It may no 

longer demonstrate a potential to address unmet needs, for example, if a new product were 

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Contains Nonbinding Recommendations

approved under a conventional approval that addressed the same needs, or if emerging clinical 

data failed to show that the product in a fast track development program had the anticipated 

advantage over existing therapy. For products in fast track drug development programs, the 

Agency expects that the appropriateness of considering particular drug development plans as part 

of the fast track program will be discussed and evaluated during the drug development process, 

including at the end of phase 2 meeting and the pre-BLA/NDA meeting. If the sponsor 

recognizes that the fast track drug development program will no longer be pursued, the sponsor 

should inform the Agency of this change in plans. 

When fast track designation is no longer supported by emerging data or the designated drug 

development program is no longer being pursued, the Agency may choose to send a letter 

notifying the sponsor that the program is no longer classified as a fast track drug development 

program. 

V. PROGRAMS FOR EXPEDITING DEVELOPMENT AND REVIEW 

It is important to distinguish between fast track designation itself and the specific programs that 

are available to a sponsor or applicant of a product in a fast track drug development program

under section 506(a) of the Act. A sponsor or applicant may apply for fast track designation at 

any time in the development process from the original submission of an IND until the BLA or 

NDA is approved by the Agency (see section IV.A.). A product that is in a fast track drug 

development program would be eligible for consideration for some or all of the programs 

outlined below. 

It is also important to recognize that, with the exception of the submission of portions of a 

BLA/NDA before submission of the entire application, the programs described below have been 

established in regulations under authority separate from section 506 of the Act. Therefore, 

products that are not in fast track drug development programs may also be able to take advantage 

of these programs. 

A. Meetings 

Appropriately timed meetings between the regulated industry and FDA are a critical aspect of 

efficient drug development. Sponsors of products in fast track drug development programs

should be in regular contact with the appropriate reviewing division to ensure that the evidence 

necessary to support marketing approval will be developed and presented in a format conducive 

to an efficient review. Specifically, the following are strongly recommended: 

1. Pre-IND consultation so that (1) appropriate preclinical studies can be performed to 

demonstrate the potential to address unmet medical needs and to support introduction of 

the product into human trials, (2) phase 1 studies can be optimally designed to support 

further product development, (3) overall development strategy can be considered, and (4) 

issues regarding the potential for fast track designation may be discussed. 

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2. An end of phase 1 meeting because, as discussed in 21 CFR 312.82 (see Appendix 3), 

the first phase 2 controlled trials in life-threatening or severely debilitating illnesses may 

provide sufficient data on safety and effectiveness to support approval, with later 

development of more extensive safety data, dose response information, and other 

information in postmarketing studies. It is critical that early trials with mortality/major 

morbidity endpoints be discussed before implementation to reach agreement on study

design, including the statistical plan. 

3. An end of phase 2 meeting to ensure that agreement between FDA and the sponsor has 

been reached on the design of the principal controlled trials intended to provide evidence 

of safety and efficacy. As noted in the paragraph above (section A.2.), for some fast

track drug development programs, a meeting with much the same purpose will occur at

the end of early clinical testing and may be referred to as end of phase 1/2 meeting. Note 

that the standard of evidence applicable to principal controlled trials is set forth at 21 

CFR 314.126 (see also the FDA guidance document, Providing Clinical Evidence of

Effectiveness for Human Drug and Biological Products). 

4. A pre-BLA/NDA meeting to discuss and achieve agreement on critical issues including: 

•

•

•

•

•

•

•

 

Whether preliminary evidence of effectiveness was seen in the principal controlled trials 

intended to provide evidence of effectiveness 

Structure, content, and timing of submission of the BLA or NDA 

Structure and content of any electronic submissions 

Structure, content, and timing of submission of portions of an application for marketing 

approval, if such submission is appropriate 

Readiness for, and proposed timing of, preapproval inspections 

Potential for, and proposed timing of, advisory committee presentation if applicable 

5. A meeting may be scheduled to discuss labeling issues as early in the review process as 

appropriate 

B. Written Correspondence 

In addition to meeting minutes,3

 the FDA should provide the sponsor with the following: 

Timely comments on the design of the proposed principal controlled clinical trials that 

are to provide the basis for the Agency's determination of the safety and effectiveness of 

the product. 

3

 Meeting minutes are part of the CBER and CDER procedures described in CBER SOPP 8101.1, Scheduling

Meetings with Regulated Industry and CDER MaPP 4512.1, Formal Meetings Between CDER and External 

Constituents. 

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End of phase 1 and/or end of phase 2 letters commenting on the adequacy of phase 2/3 

development plans 

•

•

•

•

•

•

In addition to the usual information contained in premeeting packages described in the guidance 

for industry on Formal Meetings with Sponsors and Applicants for PDUFA Products, the 

sponsor should provide the following to FDA: 

Responses to FDA questions about any clinical trials that are to form the basis for the 

Agency's determination of the safety and effectiveness of the product 

At the earliest possible time, protocols of any clinical trials that are not being carried out 

under an IND (i.e., foreign studies) and that will form the basis for the Agency's

determination of the safety and effectiveness of the product 

In meeting packages for meetings held after initial fast track designation, a discussion of 

how accumulated data and study plans continue to demonstrate that the product and the 

development plan meet the criteria for fast track designation 

If submission of portions of an incomplete application is sought, a written request for this 

kind of submission and a proposed schedule for submission (see V.C.2. below) 

As soon as possible, if there are plans to study a surrogate endpoint suitable for review 

under the accelerated approval provisions, a discussion of and support for the proposed 

endpoint 

C. Review Programs 

Sponsors of products in fast track drug development programs may be considered for one or 

more of the following procedures regarding marketing applications. 

1. Priority review of BLAs and NDAs 

Because fast track products are intended to treat serious or life-threatening conditions and must 

demonstrate the potential to address unmet medical needs for such conditions, a BLA or NDA 

for a product in a fast track drug development program ordinarily will be eligible for priority 

review (see CBER and CDER procedures in Appendix 3). 

2. Submission of portions of an application 

 a. BLAs and NDAs 

Section 506(c) of the Act provides that FDA may consider for review portions of a marketing 

application before the complete BLA or NDA is submitted. Filing may only occur if the 

applicant provides a schedule for submission of information necessary to make the application 

complete and pays any fees that may be required under section 736 of the Act (i.e., user fees). 

After the sponsor submits to the IND a preliminary evaluation of data from the clinical trials, the 

Agency may consider accepting portions of an application if (1) the clinical trials that would 

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Contains Nonbinding Recommendations

form the basis for the Agency's determination of the safety and effectiveness of the product and 

that would support drug labeling are nearing completion or have been completed, (2) the Agency 

agrees that the product continues to meet the criteria for fast track designation, and (3) the 

Agency agrees that preliminary evaluation of the clinical data supports a determination that the 

product may be effective. 

A sponsor seeking to submit portions of an application should (1) provide a schedule for 

submission of the portions of the BLA or NDA and receive FDA agreement to accept portions of 

the application and agreement that the schedule is acceptable before making any submission 

under the schedule, and (2) pay any applicable user fee to the Agency at the time the first portion 

of the BLA or NDA is submitted. The pre-BLA/NDA meeting should be used to obtain 

preliminary Agency agreement on the proposal. At the meeting, the sponsor and the reviewing 

division should discuss the data that will be used to support effectiveness, the schedule for 

submission of each portion of the BLA or NDA, and a description of portions of the application 

to be submitted separately. A request to submit portions of an application ordinarily should be 

included in the information package for the pre-BLA/NDA meeting. If a sponsor seeks to submit 

portions of an application under these procedures after the pre-BLA/NDA meeting, the sponsor 

should request submission and submit a proposed schedule for submission of portions of an 

application to the IND as soon as possible. 

A request for submission of portions of an application should be submitted as an amendment to 

the IND for the product in a fast track drug development program in triplicate with Form FDA 

1571 attached. The amendment should be clearly identified a "Request for Submission of 

Portions of an Application." A sponsor may apply for fast track designation and submission of 

portions of a BLA or NDA at the same time. These requests should be submitted as one 

amendment to the IND. 

FDA will respond to a request for submission of portions of an application by letter to the 

sponsor. Any changes in an agreement to accept portions of an application will also be in 

writing. 

b. Portions of an application eligible for early submission 

Generally, the Agency will accept for submission only a complete section of a BLA or NDA, 

such as the entire CMC section, toxicology section, or clinical section (Form FDA 356h may be 

a useful guide to items in a BLA or NDA). It is expected that a section submitted for review will 

be in a form adequate to have been included in a complete BLA or NDA submission. Drafts 

should not be included in a submission; if final reports need to be updated, the applicant should 

submit a formal amendment to the BLA or NDA with the revised information. Occasionally, the 

Agency may, in its discretion, accept less than a complete section (e.g., a CMC section lacking 

final consistency lot data and long term stability data; an acute toxicology section lacking 

chronic toxicology data; or final study reports for some or all of the principal controlled trials 

without integrated summaries) if it determines that such a subsection would constitute a 

reviewable unit and would be useful in making the review process more efficient overall. The 

company should confirm that these subsections are final reports. The Agency and the sponsor 

should work together at the time of the pre-BLA/NDA meeting to clearly define the parameters 

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Contains Nonbinding Recommendations

of accepting an incomplete section and to determine whether FDA could conduct a meaningful 

review of the submission prior to receiving the missing information. 

c. Submission of the user fee 

Section 506(c)(1) of the Act requires a sponsor to pay any fee that may be required under section 

736 of the Act before FDA may commence review of any portion of an application. The 

applicant should submit Form FDA 3397 with any applicable user fee and should follow the 

same procedures as those followed when a complete application is submitted. 

 d. Commencement of review 

Acceptance of a portion of an application by the Agency does not necessarily mean that review 

will commence or proceed prior to the receipt of a complete application. Actual commencement 

and scheduling of review will depend on many factors, including staffing, workload, competing 

priorities, time line for completion of applications, and the perceived efficiency of commencing 

review before the complete submission. 

 e. Calculation of review time

The review clock will not begin until the applicant informs the Agency that a complete BLA or 

NDA has been submitted. Following notification that the application is complete, the Agency 

will make a filing determination within the usual time (see 21 CFR 314.101).4

 3. Accelerated Approval 

Applicants whose products are in fast track drug development programs may seek traditional 

approval based on data demonstrating an effect on clinically meaningful endpoints or wellestablished surrogate endpoints. Alternatively, they may seek approval under the accelerated 

approval regulations (Appendix 4). If an applicant seeks approval of a product in a fast track 

drug development program based on evidence of an effect on a less than well-established 

surrogate endpoint, FDA may grant accelerated approval based on a determination that the effect 

on the surrogate endpoint is reasonably likely to predict clinical benefit (21 CFR 314.510 and 

601.41). Drug approval under the accelerated approval regulations may also be based on 

demonstrated clinical effects that are not the desired ultimate benefit but are reasonably likely to 

predict such benefit (e.g., improved exercise tolerance in refractory heart failure might be 

considered reasonably likely to predict ultimate benefit) (21 CFR 314.510 and 601.41). 

Section 506(b) essentially codifies in statute FDA's accelerated approval regulations. A 

surrogate endpoint was defined in the preamble to the accelerated approval rule (57 FR 13234 at 

13235, April 15, 1992) as "a laboratory or physical sign that is used in therapeutic trials as a 

substitute for a clinically meaningful endpoint that is a direct measure of how a patient feels, 

functions, or survives and that is expected to predict the effect of the therapy." Although some

surrogate endpoints are recognized as well-established and have long been a basis for approval 

 

4

 See also CBER SOPP 8404, Refuse to File Guidance for Product License Applications and Establishment License 

Applications. 

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Contains Nonbinding Recommendations

(e.g., change in blood pressure or cholesterol), the accelerated approval rule allows reliance in 

specific circumstances on a "surrogate endpoint that, while 'reasonably likely' to predict clinical 

benefit, is not so well-established as the surrogates ordinarily used as bases of approval in the 

past" (57 FR 58942 at 58944, December 11, 1992). To meet the statutory standard for approval, 

which requires the submission of "substantial evidence" to demonstrate effectiveness, "there 

must be evidence from adequate and well-controlled studies showing that the drug will have [its 

claimed] effect... That effect will, in this case, be an effect on a surrogate endpoint...." (57 FR 

58943-44). 

With respect to approval based on clinical endpoints other than survival or irreversible 

morbidity, the preamble to the final accelerated approval rule pointed out that such approval 

would usually be considered (like other approvals based on a clinical finding) under traditional 

procedures (i.e., not under accelerated approval). Approval based on clinical endpoints other 

than survival or irreversible morbidity would "be considered under the accelerated approval 

regulations only when it is essential to determine effects on survival or irreversible morbidity in 

order to confirm the favorable risk/benefit judgment that led to approval" (57 FR 58946). The 

following examples illustrate types of clinical endpoints that could be a basis for approval with a 

requirement for further studies under the provisions of the Modernization Act and the accelerated 

approval rule: 

Clinical endpoints measuring short-term benefit in a chronic condition where short-term

benefit per se does not outweigh risk and where durability of benefit is uncertain but 

expected. 

•

•

•

Clinical endpoints measuring lesser symptoms or signs of a serious disease (e.g., weight 

loss, appearance) when the resulting benefits do not per se outweigh risks but are 

expected to lead to a favorable effect on ultimate outcome, which would outweigh risks. 

Clinical endpoints measuring substantial benefits otherwise suitable for ordinary approval 

but where there exists a significant but limited concern that the treatment may adversely

affect ultimate outcome. Where such concerns are minimal, ordinary approval would be 

used. Where the concerns are substantial, data regarding ultimate outcome would be 

required preapproval. Between these extremes, accelerated approval may be considered. 

D. Dispute Resolution 

An FDA determination under the fast track program may be appealed to the reviewing division. 

If the sponsor is not satisfied with the response provided by the FDA component, the sponsor 

may elect to pursue the Agency's procedures for internal review or dispute resolution (see 21 

CFR 10.75, 312.48, and 314.103). 

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APPENDIX 1: SECTION 112 OF THE 

FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT OF 1997 

 

SEC. 112. EXPEDITING STUDY AND APPROVAL OF FAST TRACK DRUGS. 

(a) IN GENERAL- Chapter V (21 U.S.C. 351 et seq.), as amended by section 125, is 

amended by inserting before section 508 the following: 

`SEC. 506. FAST TRACK PRODUCTS. 

`(a) DESIGNATION OF DRUG AS A FAST TRACK PRODUCT- 

 `(1) IN GENERAL- The Secretary shall, at the request of the sponsor of a new 

drug, facilitate the development and expedite the review of such drug if it is intended for the 

treatment of a serious or life-threatening condition and it demonstrates the potential to address 

unmet medical needs for such a condition. (In this section, such a drug is referred to as a `fast 

track product'.) 

`(2) REQUEST FOR DESIGNATION- The sponsor of a new drug may request 

the Secretary to designate the drug as a fast track product. A request for the designation may be 

made concurrently with, or at any time after, submission of an application for the investigation of

the drug under section 505(i) or section 351(a)(3) of the Public Health Service Act. 

`(3) DESIGNATION- Within 60 calendar days after the receipt of a request under 

paragraph (2), the Secretary shall determine whether the drug that is the subject of the request 

meets the criteria described in paragraph (1). If the Secretary finds that the drug meets the 

criteria, the Secretary shall designate the drug as a fast track product and shall take such actions 

as are appropriate to expedite the development and review of the application for approval of such 

product. 

‘(b) APPROVAL OF APPLICATION FOR A FAST TRACK PRODUCT- 

`(1) IN GENERAL- The Secretary may approve an application for approval of a 

fast track product under section 505(c) or section 351 of the Public Health Service Act upon a 

determination that the product has an effect on a clinical endpoint or on a surrogate endpoint that 

is reasonably likely to predict clinical benefit. 

`(2) LIMITATION- Approval of a fast track product under this subsection may be 

subject to the requirements-- 

`(A) that the sponsor conduct appropriate post-approval studies to validate 

the surrogate endpoint or otherwise confirm the effect on the clinical endpoint; and 

`(B) that the sponsor submit copies of all promotional materials related to 

the fast track product during the preapproval review period and, following approval and for such 

period thereafter as the Secretary determines to be appropriate, at least 30 days prior to 

dissemination of the materials. 

`(3) EXPEDITED WITHDRAWAL OF APPROVAL- The Secretary may 

withdraw approval of a fast track product using expedited procedures (as prescribed by the 

Secretary in regulations which shall include an opportunity for an informal hearing) if-- 

 `(A) the sponsor fails to conduct any required post-approval study of the 

fast track drug with due diligence; 

`(B) a post-approval study of the fast track product fails to verify clinical 

benefit of the product; 

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Contains Nonbinding Recommendations

 `(C) other evidence demonstrates that the fast track product is not safe or 

effective under the conditions of use; or 

`(D) the sponsor disseminates false or misleading promotional materials 

with respect to the product. 

‘(c) REVIEW OF INCOMPLETE APPLICATIONS FOR APPROVAL OF A FAST 

TRACK PRODUCT- 

`(1) IN GENERAL- If the Secretary determines, after preliminary evaluation of 

clinical data submitted by the sponsor, that a fast track product may be effective, the Secretary 

shall evaluate for filing, and may commence review of portions of, an application for the 

approval of the product before the sponsor submits a complete application. The Secretary shall 

commence such review only if the applicant-- 

`(A) provides a schedule for submission of information necessary to make 

the application complete; and 

`(B) pays any fee that may be required under section 736. 

`(2) EXCEPTION- Any time period for review of human drug applications that 

has been agreed to by the Secretary and that has been set forth in goals identified in letters of the 

Secretary (relating to the use of fees collected under section 736 to expedite the drug 

development process and the review of human drug applications) shall not apply to an 

application submitted under paragraph (1) until the date on which the application is complete. 

‘(d) AWARENESS EFFORTS- The Secretary shall-- 

`(1) develop and disseminate to physicians, patient organizations, pharmaceutical 

and biotechnology companies, and other appropriate persons a description of the provisions of 

this section applicable to fast track products; and 

`(2) establish a program to encourage the development of surrogate endpoints that 

are reasonably likely to predict clinical benefit for serious or life-threatening conditions for 

which there exist significant unmet medical needs.'.

(b) GUIDANCE- Within 1 year after the date of enactment of this Act, the Secretary of 

Health and Human Services shall issue guidance for fast track products (as defined in section 

506(a)(1) of the Federal Food, Drug, and Cosmetic Act) that describes the policies and 

procedures that pertain to section 506 of such Act. 

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APPENDIX 2: PROCEDURES FOR DRUGS INTENDED TO TREAT 

LIFE-THREATENING AND SEVERELY DEBILITATING ILLNESSES 

21 CFR Parts 312 and 314 

Investigational New Drug, Antibiotic and Biological Drug Product Regulations; 

Procedures for Drugs Intended to Treat Life-Threatening 

and Severely Debilitating Illnesses; Interim Rule 

(53 Federal Register 41516, October 21, 1998) 

(Attachment provided separately) 

 

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Contains Nonbinding Recommendations

APPENDIX 3: PRIORITY REVIEW POLICIES 

Center for Biologics Evaluation and Research 

Manual of Standard Operating Procedures and Policies 

SOPP 8405, Complete Review and Issuance of Action Letters, June 11, 1998 

Center for Drug Evaluation and Research 

Manual of Policies and Procedures 

MaPP 6020.3, Priority Review Policy, April 22, 1996 

(Attachment provided separately) 

 

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20

APPENDIX 4: ACCELERATED APPROVAL OF NEW DRUGS AND BIOLOGICAL 

PRODUCTS FOR SERIOUS OR LIFE-THREATENING ILLNESSES 

21 CFR 314 and 601 

New Drug, Antibiotic, and Biological Drug Product Regulations; 

Accelerated Approval; Final Rule 

(57 Federal Register 58942, December 11, 1992) 

(Attachment provided separately)