ANTIBIOTICS

FDA Has Encouraged 

Development, but 

Needs to Clarify the 

Role of Draft 

Guidance and 

Develop Qualified 

Infectious Disease 

Product Guidance

Report to Congressional Requesters

January 2017

GAO-17-189

United States Government Accountability Office
United States Government Accountability Office

Highlights of GAO-17-189, a report to

congressional requesters

January 2017

ANTIBIOTICS

FDA Has Encouraged Development, but Needs 

to Clarify the Role of Draft Guidance and 

Develop Qualified Infectious Disease Product 

Guidance

What GAO Found

The Food and Drug Administration (FDA) released updated or new guidance for 

antibiotic development, and used the qualified infectious disease products 

(QIDP) designation to encourage the development of new antibiotics. As of 

August 2016, FDA, an agency within the Department of Health and Human 

Services (HHS), had coordinated the release of 14 updated or new guidance 

documents on antibiotic development, in compliance with Generating Antibiotic 

Incentives Now (GAIN) provisions of the Food and Drug Administration Safety 

and Innovation Act of 2012. However, half of these guidance documents remain 

in draft form. The GAIN provisions required FDA to review and, as appropriate, 

revise guidance documents related to antibiotics, in part to ensure that they

reflected scientific developments. FDA used the QIDP designation and its 

incentives, created under the GAIN provisions, to encourage drug sponsors to

develop new antibiotics. Incentives available under the QIDP designation include 

eligibility for fast track designation—which allows drug sponsors to have 

increased interaction with FDA and allows FDA to review portions of sponsors’ 

applications as they come in rather than waiting for a complete application. FDA 

granted 101 out of 109 requests for the QIDP designation from July 2012, when 

the designation was created, through December 2015. FDA also approved six 

drugs with the QIDP designation for market in the United States.

The 10 drug sponsors in GAO’s study said that GAIN has facilitated FDA’s 

review of their drug applications, and 8 said they experienced increased 

communication with FDA due to the agency’s implementation of GAIN and 

general commitment to supporting the development of new antibiotics. However, 

several were uncertain whether they could rely on FDA’s draft guidance or were 

concerned about the lack of guidance describing the QIDP designation and its 

requirements. For example, 2 drug sponsors expressed concern about the role

of FDA’s draft guidance. A third sponsor said it would be helpful if certain draft 

guidance was finalized. Five additional drug sponsors in GAO’s study stated that 

written guidance from FDA related to the QIDP designation and its incentives, 

such as the process for obtaining fast track designation for a QIDP-designated

application, would help them to better understand the requirements and its 

associated benefits. FDA released some of its updated guidance documents in 

draft form on its website, in response to GAIN, which indicated that they were 

intended for comment purposes only, not for implementation, and would 

represent the agency’s current thinking “when finalized.” While these draft 

guidance documents can include updated information, it is unclear if the new 

information represents FDA’s current thinking on a topic or if the purpose of the 

draft guidance is limited to generating public comment. Internal control standards

for the federal government on information and communication state that sharing 

quality information with external parties is necessary to achieving an entity’s 

objectives. The lack of clarity on the role of draft guidance for and the lack of 

written guidance on the QIDP designation create uncertainty for drug sponsors 

about how much reliance they should place on these draft documents and could 

diminish the likelihood that drug sponsors apply for the designation because they 

do not fully understand its requirements and benefits. View GAO-17-189. For more information, 

contact John E. Dicken at (202) 512-7114 or 

dickenj@gao.gov.

Why GAO Did This Study

Antibiotics have long played a key role 

in treating infections, but this role is 

threatened by growing resistance to 

existing antibiotics and the decline in 

the development of new drugs. FDA

oversees the approval of drugs for the 

U.S. market. The GAIN provisions 

created the QIDP designation and its 

associated incentives to encourage the 

development of new drugs to treat

serious or life-threatening infections. 

While it is too soon to tell if GAIN has 

stimulated the development of new 

drugs, GAO was asked to provide 

information on FDA’s efforts to 

implement GAIN. This report examines 

(1) steps FDA has taken to encourage 

the development of antibiotics since 

GAIN, and (2) drug sponsors’ 

perspectives on FDA’s efforts. GAO 

analyzed FDA data on requests for the 

QIDP designation from July 2012

through December 2015 (the most 

recent data available at the time of 

GAO’s review), and on drugs approved 

with this designation during the same 

time frame. GAO reviewed relevant 

FDA guidance documents and internal 

controls. GAO interviewed FDA 

officials and obtained information from 

a nongeneralizable selection of 10

drug sponsors about FDA efforts.

What GAO Recommends

GAO recommends that FDA clarify the 

role of draft guidance for and develop 

written guidance on the QIDP 

designation to help drug sponsors 

better understand the designation and 

its associated incentives. HHS said it 

would consider GAO’s first 

recommendation and agreed with the 

second. GAO believes the first 

recommendation should also be 

adopted.
Page i GAO-17-189 FDA Qualified Infectious Disease Products

Letter 1

Background 4

FDA Created a Task Force to Coordinate the Release of 

Guidance and Used the QIDP Designation to Encourage the 

Development of New Antibiotics 8

Drug Sponsors in Our Study Said That GAIN Has Facilitated 

FDA’s Review of Their Antibiotic Applications, but Also 

Expressed Concern about Available Guidance 17

Conclusions 21

Recommendations for Executive Action 22

Agency Comments and Our Evaluation 22

Appendix I Additional Food and Drug Administration (FDA) Antimicrobial 

Resistance Efforts 24

Appendix II Antibiotic-Related Guidance Documents Released by the Food 

and Drug Administration 26

Appendix III Comments from the Department of Health & Human Services 29

Appendix IV GAO Contact and Staff Acknowledgments 31

Tables

Table 1: Food and Drug Administration (FDA) Incentives Available 

to Eligible Drug Applications and Associated with the 

Qualified Infectious Disease Products (QIDP) Designation 7

Table 2: Guidance Documents on Antibiotics Released by the 

Food and Drug Administration (FDA) Since Generating 

Antibiotic Incentives Now (GAIN), as of August 2016 10

Table 3: Number and Percentage of Granted Requests for the 

Food and Drug Administration’s (FDA) Qualified Infectious 

Disease Products (QIDP) Designation, July 9, 2012, 

through December 31, 2015 14

Contents
Page ii GAO-17-189 FDA Qualified Infectious Disease Products

Table 4: Number of Requests and Requests Granted for the 

Qualified Infectious Disease Products (QIDP) and Fast 

Track Designations Granted by the Food and Drug 

Administration (FDA), July 9, 2012, through December 31, 

2015 15

Table 5: Food and Drug Administration (FDA) Drugs Approved 

with the Qualified Infectious Disease Products (QIDP) 

Designation, as of October 2016 16

Abbreviations

ABSSSI acute bacterial skin and skin structure infections

FDA Food and Drug Administration

FDASIA Food and Drug Administration Safety and Innovation Act 

GAIN Generating Antibiotic Incentives Now 

HABP/VABP hospital-acquired and ventilator-associated bacterial

pneumonia 

HHS Department of Health and Human Services

QIDP qualified infectious disease products

This is a work of the U.S. government and is not subject to copyright protection in the 

United States. The published product may be reproduced and distributed in its entirety 

without further permission from GAO. However, because this work may contain 

copyrighted images or other material, permission from the copyright holder may be 

necessary if you wish to reproduce this material separately.
Page 1 GAO-17-189 FDA Qualified Infectious Disease Products

441 G St. N.W.

Washington, DC 20548

January 31, 2017

The Honorable Lamar Alexander

Chairman

Committee on Health, Education, Labor, and Pensions

United States Senate

The Honorable Richard Burr

United States Senate

Antibiotics have long played an important role in the care and well-being 

of people with various types of infections. However, this role is threatened 

by the growing resistance of bacteria to existing antibiotics and the steady 

decline in the development of new antibiotics since the 1980s. More than 

2 million people are sickened every year in the United States with 

antibiotic-resistant infections, with at least 23,000 dying as a result.1 The 

number of new antibiotics approved for prescription use in the United 

States has declined from 29 in the 1980s to 9 in the first decade of the 

2000s.2 The limited number of antibiotics under development is a matter 

of concern for the Food and Drug Administration (FDA), the agency within 

the Department of Health and Human Services (HHS) responsible for the 

approval of drugs for market in the United States.

In 2012, Congress passed the Food and Drug Administration Safety and 

Innovation Act (FDASIA), title VIII of which is commonly referred to as the 

Generating Antibiotic Incentives Now (GAIN) provisions.3 The GAIN 

provisions required FDA to take certain steps to encourage drug sponsors 

to develop qualified infectious disease products (QIDP), intended for the 

 1

Department of Health and Human Services, Centers for Disease Control and Prevention, 

Antibiotic Resistance Threats in the United States, 2013 (Atlanta, Ga.: Sept. 16, 2013), 

accessed December 3, 2015, http://www.cdc.gov/drugresistance/threat-report-2013/.

2

The Pew Charitable Trusts, A Scientific Roadmap for Antibiotic Discovery (Washington, 

D.C.: May 2016), accessed September 23, 2016, 

http://www.pewtrusts.org/~/media/assets/2016/05/ascientificroadmapforantibioticdiscovery

.pdf. 

3

Food and Drug Administration Safety and Innovation Act, Pub. L. No. 112-144, §§ 801 et 

seq., 126 Stat. 993, 1077 (2012). 

Letter
Page 2 GAO-17-189 FDA Qualified Infectious Disease Products

treatment of serious or life-threatening infections.4 However, it is too soon 

to determine if the GAIN provisions have actually stimulated the 

development of new antibiotics. FDA has taken steps to implement these 

provisions and drug sponsors have applied for and received the QIDP 

designation for drugs already in development. The GAIN provisions were 

passed 5 years ago, but it generally takes 10 to 15 years to develop a 

new drug and obtain approval from FDA.5 Therefore, GAIN has not been 

in place long enough yet to have been a factor in motivating any drug 

sponsor to develop and submit an application to FDA to market a new 

antibiotic.

You asked us to provide information on FDA’s implementation of the 

GAIN provisions. This report examines

1. the steps FDA has taken to encourage the development of antibiotics 

to treat serious or life-threatening infections since the enactment of 

GAIN, and

2. drug sponsors’ perspectives on FDA’s efforts to encourage the 

development of antibiotics to treat serious or life-threatening infections 

since the enactment of GAIN.

To examine the steps FDA has taken to encourage the development of 

antibiotics to treat serious or life-threatening infections since GAIN, we 

reviewed the GAIN provisions included in FDASIA. We also reviewed 

FDA guidance documents related to antibiotic drug development and 

unmet medical need identified by the agency as being related to GAIN.6

We analyzed FDA data on drug sponsors’ requests to FDA to obtain the 

QIDP designation and the number of requests FDA granted from July 9, 

 4

A drug sponsor is a person or entity, such as a drug company, that takes responsibility 

for developing a drug. To do this, the drug sponsor must comply with applicable laws and 

regulations. GAIN defines a QIDP as an antibacterial or antifungal drug for human use 

intended to treat serious or life-threatening infections. Pub. L. No. 112-144, § 801, 126 

Stat. 1077 (codified in pertinent part at 21 U.S.C. § 355f(g)). For the purposes of this 

report, we use the term antibiotics to refer to substances that are able to inhibit or kill 

bacteria to treat an infection (i.e., antibacterials). GAIN also refers to certain antifungals—

substances that are able to inhibit or kill fungi. Thus, we use the term antibiotics to refer to 

both antibacterials and antifungals. While not as prominent an issue as with antibacterials, 

antifungals face similar challenges with resistance and the need for new drugs. 

5

Pharmaceutical Research and Manufacturers of America, 2016 Biopharmaceutical 

Research Industry Profile (Washington, D.C.: April 2016).

6

FDA defines unmet medical need as a condition whose treatment or diagnosis is not 

addressed adequately by available therapy. 
Page 3 GAO-17-189 FDA Qualified Infectious Disease Products

2012, (when the QIDP designation was created) through December 31, 

2015, (the most current available data at the time of our review). We 

limited the requests that we examined to those associated with new 

antibiotic drug applications and did not include applications for other types 

of products.7 We also reviewed FDA data on the six drugs the agency 

approved with the QIDP designation; these data included information 

such as the drug’s proprietary name and indication for use.8 We assessed 

the reliability of these data by, for example, conducting data checks and 

interviewing knowledgeable FDA officials about the data. We determined 

that these data were sufficiently reliable for the purposes of our reporting 

objectives. We also interviewed FDA officials on their efforts to encourage 

the submission of new drug applications by implementing GAIN.

To examine drug sponsors’ perspectives on FDA’s efforts to encourage 

the development of antibiotics to treat serious or life-threatening infections 

since GAIN, we contacted certain industry stakeholders for their 

assistance in identifying drug sponsors to include in our study. 

Information about FDA’s review of drug sponsors’ applications, including 

information about whether a drug sponsor is seeking a QIDP designation 

and FDA’s subsequent decision, is proprietary. Therefore, we asked two 

organizations that represent drug sponsors and two organizations that 

conduct research in the area of antibiotic innovation to ask drug sponsors 

who had experience with FDA’s QIDP designation or antibiotic drug 

development generally to participate in our study. Eight drug sponsors 

agreed to participate—6 of which we interviewed and 2 of which 

answered our questions in writing. Two of these 8 drug sponsors had 

drugs approved with the QIDP designation. Because there are a total of 4 

sponsors that had drugs approved with the QIDP designation and we 

wanted to interview all of them, we contacted the other 2 drug sponsors, 

both of which agreed to participate in our study. The 10 drug sponsors in 

our study had different characteristics; for example, they included large 

and small drug sponsors, those with approved antibiotics, and those with 

 7

That is, the requests we reviewed were limited to requests for antibiotics and did not 

include requests for other types of products to which the GAIN provisions do not apply and 

are therefore not eligible for the QIDP designation, such as antivirals, or for biologic 

license applications. Antivirals are drugs that can prevent or reduce the severity of a viral 

infection, such as influenza. Biologic license applications are applications for approval of 

biologic products, such as vaccines. 

8

Indication for use refers to the intended use for which a drug was approved by FDA, 

including the treatment, prevention, mitigation, cure, or diagnosis of a recognized disease 

or condition or for the relief of symptoms associated with a recognized disease or 

condition. 
Page 4 GAO-17-189 FDA Qualified Infectious Disease Products

antibiotics in development that have a QIDP designation, according to 

publicly available data. These drug sponsors’ perspectives are not 

generalizable to all drug sponsors. We supplemented our understanding 

of drug sponsors’ perspectives by analyzing FDA data on review times for 

approved antibiotics with the QIDP designation from July 9, 2012, through 

December 31, 2015. To assess the reliability of these data, we reviewed 

relevant documentation, conducted data checks, and interviewed 

knowledgeable FDA officials about the data. We determined that these 

data were sufficiently reliable for the purposes of our reporting objectives. 

We also reviewed FDA guidance related to other expedited programs that 

FDA implements, including programs for which antibiotics qualify, to 

understand what information the agency provides about the features and 

benefits of these programs. Lastly, we compared the relevant federal 

internal control standards related to information sharing and 

communication with FDA’s guidance and other communications with drug 

sponsors about the QIDP designation.9

We conducted this performance audit from December 2015 to January 

2017 in accordance with generally accepted government auditing

standards. Those standards require that we plan and perform the audit to 

obtain sufficient, appropriate evidence to provide a reasonable basis for 

our findings and conclusions based on our audit objectives. We believe 

that the evidence obtained provides a reasonable basis for our findings 

and conclusions based on our audit objectives.

Antibiotics are drugs used to treat bacterial infections; antibiotic 

resistance is the result of changes in bacteria that reduce or eliminate the 

effectiveness of antibiotics to treat infection. Experts have raised 

concerns about the lack of new antibiotics being developed to replace 

antibiotics that have become ineffective because of resistance.10 This lack 

of development has been attributed to various challenges. For example, 

the development of new drugs, including antibiotics, is often a costly and 

lengthy process. To obtain FDA’s approval to market a new drug, a drug 

 9

GAO, Standards for Internal Control in the Federal Government, GAO-14-704G 

(Washington, D.C.: Sept. 10, 2014). Internal control is a process effected by an entity’s 

oversight body, management, and other personnel that provides reasonable assurance 

that the objectives of an entity will be achieved.

10Executive Office of the President, President’s Council of Advisors on Science and 

Technology, Report to the President on Combating Antibiotic Resistance (Washington, 

D.C.: September 2014). 

Background
Page 5 GAO-17-189 FDA Qualified Infectious Disease Products

sponsor must conduct extensive research in order to demonstrate that the 

drug is both safe and effective. Although high costs and failure rates 

make drug development risky for drug sponsors, creating a safe and 

effective new drug can be financially rewarding for the drug sponsor and 

beneficial to the public. However, antibiotics are often less profitable than 

other drugs because they are generally designed to work quickly and are 

typically administered for only a brief time.

FDA oversees the drug development process and the approval of new 

drugs for marketing in the United States.11 FDA generally reviews drug 

sponsors’ plans for conducting clinical trials and assesses drug sponsors’ 

applications for the approval of new antibiotics. FDA also releases 

guidance for industry as a way to communicate its current thinking on a 

particular topic with the purpose of assisting drug sponsors in the 

development of drugs. For example, FDA has released several guidance 

documents to assist drug sponsors with the development of antibiotics, 

including information on designing clinical trials and measures to 

demonstrate a drug’s effectiveness.

The GAIN provisions required FDA to take certain steps to encourage 

drug sponsors to develop antibiotics, particularly those that treat serious 

or life-threatening infections. Specifically, FDA was required each year to 

review, and revise as appropriate, at least three guidance documents 

related to the development of antibiotics.12 FDA was also required to 

finalize a guidance document on the development of antibacterial drugs 

for serious or life-threatening infections, particularly in areas of unmet 

medical need.13 The GAIN provisions also established the QIDP 

designation and made incentives available to sponsors of QIDPs—fast 

 11Within FDA, the Center for Drug Evaluation and Research is responsible for ensuring 

the safety and efficacy of drugs, including antibiotics. The Center also regulates certain 

biologics for human use, such as monoclonal antibodies targeting particular pathogens 

and associated toxins. These biologics were beyond the scope of this report.

12Pub. L. No. 112-114, § 804, 126 Stat. 1080 (codified in pertinent part at 21 U.S.C. § 

360a-1(a)). 

13Pub. L. No. 112-144, § 806, 126 Stat. 1082 (codified at 21 U.S.C. § 355 note)).
Page 6 GAO-17-189 FDA Qualified Infectious Disease Products

track designation, priority review designation, and 5 years of additional 

market exclusivity.14

• Fast track designation may expedite FDA’s review of an application by 

allowing drug sponsors to have increased communication with FDA 

and by allowing FDA to review portions of the application as they 

come in rather than waiting for a complete application. Although drug 

sponsors that receive QIDP designation are also entitled to receive 

fast track designation, drug sponsors must still request this 

designation and typically do so prior to submitting their application to 

FDA for review.

• Priority review has been automatically granted to applications with the 

QIDP designation. It reduces FDA’s goal time for the review of an 

application from 10 months to 6 months.15

• Market exclusivity is a statutory provision for exclusive marketing 

rights for certain periods upon approval of a drug application, if certain 

statutory requirements are met.16 Market exclusivity periods last 

different lengths of time and have different scopes. For example, 

drugs designated for treatment of rare diseases or conditions may be 

eligible for orphan drug exclusivity, which lasts for 7 years for the 

 14Pub. L. No. 112-144, §§ 801-803, 126 Stat. 1077-1079, (codified in pertinent part at 21 

U.S.C. §§ 355f (a), (d) (additional exclusivity and QIDP designation), 360n-1 (priority 

review), 356 (b) (fast track)). The GAIN provisions included other provisions requiring FDA 

to establish a list of pathogens that have the potential to pose a serious threat to public 

health and issue a report to Congress on the agency’s implementation of the GAIN 

provisions in 2017. See, Pub. L. No. 112-144, §§ 801(f) (2), 805, 126 Stat. 1078, 1080 

(codified at 21 U.S.C. §§ 355f (f) (pathogens)). This report does not discuss those 

provisions.

15According to FDA, all QIDP drugs approved to date have contained a new molecular 

entity, which is an active ingredient that contains no active moieties that have been 

previously approved by the agency or have been previously marketed as a drug in the 

United States. Active moieties are certain molecules or ions responsible for the 

physiological or pharmacological action of the drug substance. For new molecular entities, 

FDA’s goal is to review and act on an application within 10 months of the 60 calendar day 

filing review period that begins on the date of FDA’s receipt of the original drug application 

(a total of 12 months). Priority review reduces this time to 6 months of the 60 day filing 

date (a total of 8 months).

16Market exclusivity and patents are similar in that they provide drug sponsors certain 

marketing protection of new products. However, instead of automatically receiving market 

exclusivity from FDA as described above, drug sponsors file for patents with the United 

States Patent and Trademark Office and may do so at any time during the development of 

a drug. A patent is a property right issued by the United States Patent and Trademark 

Office, can encompass a wide range of claims, and according to FDA, a drug patent 

generally expires 20 years after the date on which it was filed. 
Page 7 GAO-17-189 FDA Qualified Infectious Disease Products

specified conditions. New chemical entity exclusivity provides 5 years 

of market exclusivity if a drug includes a new active moiety that has 

not been previously approved by FDA. QIDP-related market

exclusivity adds an additional 5 years of exclusivity to certain 

qualifying drugs. For example, a drug receiving orphan drug 

exclusivity receives 7 years of exclusivity. If that drug’s application 

also received a QIDP designation, then the drug may receive an 

additional 5 years of exclusivity, for a total of 12 years of market 

exclusivity. Table 1 provides more information on the different 

incentives associated with the QIDP designation.

Table 1: Food and Drug Administration (FDA) Incentives Available to Eligible Drug Applications and Associated with the 

Qualified Infectious Disease Products (QIDP) Designation

Incentives Description

Fast track designation This designation facilitates drug sponsors increased communication with FDA and may 

include a rolling review of application materials—that is, FDA reviews portions of the 

application as they come in instead of waiting for the complete application before beginning 

its review.

Although a QIDP designation entitles a drug sponsor to also receive fast track designation, a 

drug sponsor must still request fast track designation from FDA. A drug sponsor generally 

requests this designation during the drug’s development and testing stage, before the 

submission of an application to FDA for approval for marketing. 

Priority review designation Priority review reduces FDA’s goal time for taking action on a drug application from 10 

months to 6 months.a FDA will automatically grant this designation to the first application 

submitted for approval for a QIDP-designated drug, and does not require the sponsor to 

request it.

Market exclusivity If a drug application meets certain statutory requirements, market exclusivity may delay 

approval of certain competing drug applications. There are different types of exclusivity for 

different lengths of time and scopes.

A drug sponsor may receive 5 years of additional market exclusivity for its drug if the drug 

with QIDP designation was previously approved by FDA and was eligible for another type of 

exclusivity. For example, a drug designated for treatment of rare diseases or conditions may 

receive 7 years of orphan drug exclusivity for the specified conditions. If that drug’s 

application also received a QIDP designation, then the drug could receive an additional 5 

years of exclusivity, for a total of 12 years of market exclusivity. 

Source: GAO analysis of the Generating Antibiotic Incentives Now provisions and FDA information. │ GAO-17-189

Note: FDA may grant fast track designation and priority review individually or in combination to drug 

sponsors whose applications are not for antibiotics and did not receive a QIDP designation, but 

otherwise meet the criteria for one or more of these programs.

a

According to FDA, all QIDP drugs approved to date have contained a new molecular entity, which is 

an active ingredient that contains no active moieties that have been previously approved by the 

agency or have been previously marketed as a drug in the United States. Active moieties are certain

molecules or ions responsible for the physiological or pharmacological action of the drug substance. 

For new molecular entities, FDA’s goal is to review and act on an application within 10 months of the 

60 calendar day filing review period that begins on the date of FDA’s receipt of the original drug 

application (a total of 12 months). Priority review reduces this time to 6 months of the 60 day filing 

date (a total of 8 months).
Page 8 GAO-17-189 FDA Qualified Infectious Disease Products

In 2012, FDA created an internal group called the Antibacterial Drug 

Development Task Force (Task Force) to coordinate the release of 

guidance documents for antibiotics as part of its role to promote the 

development of these types of drugs.17 The GAIN provisions required 

FDA to review and revise each year, as appropriate, at least three 

guidance documents related to antibiotics, in part to ensure the 

documents reflected scientific developments. FDA officials also reviewed 

the list of available guidance documents and released guidance on new 

topics, where needed. Established after the passage of the GAIN 

provisions, the Task Force is a multidisciplinary group that comprises 

scientists and clinicians who participate in FDA’s oversight of the drug 

development process. Members of this Task Force work with experts, 

such as those from academia, industry, and professional societies, and 

with patient advocacy groups, to promote the development of new 

antibiotics.

As of August 2016, FDA and the Task Force had coordinated the release 

of 14 updated or new guidance documents related to the development of 

antibiotics, although half of these documents remain in draft form.18 Table 

 17This Task Force is specific to FDA’s Center for Drug Evaluation and Research, the 

Center within FDA responsible for reviewing and approving drug applications. FDA has an 

agency-wide task force called the Antimicrobial Resistance Task Force that focuses its 

efforts more broadly on antimicrobial resistance issues. Other Centers within FDA, such 

as the Center for Biologics Evaluation and Research and the Center for Devices and 

Radiological Health, also engage in similar activities. For more information on the 

Antimicrobial Task Force and these other Centers’ activities, see app. I of this report. 

18According to FDA, FDA review staff reviewed and revised most of these guidance 

documents. Officials said the Task Force was consulted for “scientifically challenging” 

guidance documents, such as guidance on hospital-acquired and ventilator-associated 

bacterial pneumonia.

FDA Created a Task 

Force to Coordinate 

the Release of 

Guidance and Used 

the QIDP Designation 

to Encourage the 

Development of New 

Antibiotics

FDA Created a Task Force 

to Coordinate the Release 

of Guidance Documents 

for Antibiotics
Page 9 GAO-17-189 FDA Qualified Infectious Disease Products

2 lists guidance documents for antibiotics that FDA released in 

accordance with the GAIN provisions. Half of these 14 documents were 

finalized versions of prior draft guidance documents, such as FDA’s 2015 

guidance on uncomplicated gonorrhea.19 FDA released the remaining 

guidance documents in draft form—specifically, the guidance either 

updated a prior draft guidance or was a brand new draft guidance for a 

new topic. For example, FDA’s most recent draft guidance on bacterial 

vaginosis, released in July 2016, is an update to prior draft guidance from 

July 1998, while FDA’s draft guidance on pulmonary tuberculosis, 

released in November 2013, is the first guidance on this topic FDA has 

released.20 FDA made these draft guidance documents publicly available 

on its website, in keeping with the agency’s good guidance practices. 

According to FDA, these draft guidance documents are made available to 

encourage public comment. Further, the draft guidance documents on 

developing antibiotics we examined indicated on the title page and on 

subsequent pages that they were intended for comment purposes only, 

not for implementation, and would represent the agency’s current thinking 

“when finalized.”21 Thus, because the draft documents on the FDA 

website for public comment have not been finalized, drug sponsors are 

left without written guidance indicating FDA’s current thinking on a given 

issue until the agency finalizes the guidance. As of January 2017, FDA 

had not responded to questions we provided in June 2016 about why 

some guidance documents remain in draft form or whether drug sponsors 

 19Department of Health and Human Services, Food and Drug Administration, 

Uncomplicated Gonorrhea: Developing Drugs for Treatment Guidance for Industry (Silver 

Spring, Md.: August 2015). In July 2014, FDA finalized guidance on developing drugs to 

treat neglected tropical diseases. See Department of Health and Human Services, Food 

and Drug Administration, Guidance for Industry Neglected Tropical Diseases of the 

Developing World: Developing Drugs for Treatment or Prevention (Silver Spring, Md.: July 

2014). According to FDA officials, while this guidance document is not specifically in 

response to GAIN, some of the drugs intended to treat neglected tropical diseases overlap 

with QIDPs. Neglected tropical diseases are infectious diseases that generally are rare or 

absent in developed countries, but are often widespread in the developing world. 

20Department of Health and Human Services, Food and Drug Administration, Bacterial 

Vaginosis: Developing Drugs for Treatment Guidance for Industry (Draft) (Silver Spring, 

Md.: July 2016); Guidance for Industry: Bacterial Vaginosis—Developing Antimicrobial 

Drugs for Treatment (Draft) (Rockville, Md.: July 1998); and Guidance for Industry 

Pulmonary Tuberculosis: Developing Drugs for Treatment (Draft) (Silver Spring, Md.: 

November 2013).

21According to FDA, the agency generally announces the release of draft guidance 

documents for public comment in the Federal Register. Guidance documents represent 

FDA’s current thinking on a topic. Neither draft nor final guidance documents legally bind 

FDA or confer legal rights on affected individuals. See 21 C.F.R. § 10.115 (2016). 
Page 10 GAO-17-189 FDA Qualified Infectious Disease Products

should rely on draft guidance documents while developing their drugs. 

FDA informed us that its responses were in agency clearance. FDA also 

had previously received a similar request from Congress and told us it 

would provide responses to us and to Congress simultaneously when the 

responses are finalized. FDA did not indicate when those responses 

would be finalized and provided to us.

Table 2: Guidance Documents on Antibiotics Released by the Food and Drug Administration (FDA) Since Generating 

Antibiotic Incentives Now (GAIN), as of August 2016

Guidance title Release date Updated draft 

guidance

New draft 

guidance

Finalized 

guidancea

Bacterial Vaginosis: Developing Drugs for Treatment 

Guidance for Industry

July 2016 ✓

Vulvovaginal Candidiasis: Developing Drugs for 

Treatment Guidance for Industry

July 2016 ✓

Anthrax: Developing Drugs for Prophylaxis of 

Inhalation Anthrax Guidance for Industry

February 2016 ✓

Uncomplicated Gonorrhea: Developing Drugs for 

Treatment Guidance for Industry

June 2014 (updated 

draft)

August 2015

(finalized)

✓ ✓

Complicated Urinary Tract Infections: Developing 

Drugs for Treatment Guidance for Industry 

February 2015 ✓

Complicated Intra-Abdominal Infections: Developing 

Drugs for Treatment Guidance for Industry

October 2012

(new draft)

February 2015

(finalized)

✓ ✓

Guidance for Industry Hospital-Acquired Bacterial 

Pneumonia and Ventilator-Associated Bacterial 

Pneumonia: Developing Drugs for Treatment

May 2014 ✓

Guidance for Industry Community-Acquired Bacterial 

Pneumonia: Developing Drugs for Treatment

January 2014 ✓

Guidance for Industry Pulmonary Tuberculosis: 

Developing Drugs for Treatment

November 2013 ✓

Guidance for Industry Acute Bacterial Skin and Skin 

Structure Infections: Developing Drugs for Treatment

October 2013 ✓

Guidance for Industry Antibacterial Therapies for 

Patients with Unmet Medical Need for the Treatment of 

Serious Bacterial Diseases

July 2013 ✓

Guidance for Industry Acute Bacterial Sinusitis: 

Developing Drugs for Treatment

October 2012 ✓
Page 11 GAO-17-189 FDA Qualified Infectious Disease Products

Guidance title Release date Updated draft 

guidance

New draft 

guidance

Finalized 

guidancea

Guidance for Industry Acute Bacterial Exacerbations of 

Chronic Bronchitis in Patients with Chronic Obstructive 

Pulmonary Disease: Developing Antimicrobial Drugs 

for Treatment 

September 2012 ✓

Guidance for Industry Acute Bacterial Otitis Media: 

Developing Drugs for Treatment

September 2012 ✓

Source: FDA. │ GAO-17-189

Note: Under the GAIN provisions in the FDA Safety and Innovation Act of 2012, FDA is required each 

year to review and, as appropriate revise, at least three guidance documents. See app. II for a list of 

these guidance documents with full citations.

a

These guidance documents were initially issued as draft guidance and subsequently finalized, in 

accordance with the agency’s good guidance practices.

According to FDA officials, they selected the antibiotic-related guidance to 

review, and potentially revise, for various reasons, such as the 

emergence of new scientific information. Officials said that they also 

coordinate with external stakeholders on identifying and addressing 

challenges to antibiotic development, such as consulting with them about 

any changes they make to guidance documents. For example, FDA 

participated in meetings with the Foundation for the National Institutes of 

Health and worked with the Clinical Trials Transformation Initiative when it 

revised two of its guidance documents on developing drugs to treat acute 

bacterial skin and skin structure infections (ABSSSI) and on drug 

development for hospital-acquired and ventilator-associated bacterial 

pneumonia (HABP/VABP).22

• In 2013, FDA finalized its revision of a 2010 draft guidance document 

on developing drugs to treat ABSSSI based, in part, on work on 

clinical endpoints conducted by the Foundation for the National 

Institutes of Health.23 Differences between the finalized 2013 

 22The Foundation for the National Institutes of Health coordinates with public and private 

institutions in support of the mission of the National Institutes of Health to, for example, 

accelerate biomedical research. The Clinical Trials Transformation Initiative comprises 

more than 70 organizations, including government agencies, drug sponsors, patient 

advocacy and professional groups, and academic institutions, and works to develop and 

promote practices that will increase the quality and efficiency of clinical trials. 

23Department of Health and Human Services, Food and Drug Administration, Guidance 

for Industry Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for 

Treatment (Silver Spring, Md.: October 2013) and Guidance for Industry Acute Bacterial 

Skin and Skin Structure Infections: Developing Drugs for Treatment (Draft) (Silver Spring, 

Md.: August 2010). Clinical endpoints in clinical trials are measures used to determine if 

there is a statistically significant difference between two treatments being compared.
Page 12 GAO-17-189 FDA Qualified Infectious Disease Products

document and the draft 2010 document included changes in the 

minimum number of clinical trials FDA recommended that a drug 

sponsor conduct and the clinical endpoints FDA recommended that a 

sponsor use to assess the effectiveness of a drug. The 2010 guidance 

document recommended that drug sponsors conduct at least two 

adequate and well-controlled trials. When FDA released the finalized 

guidance in 2013, the agency noted that drug sponsors could also 

provide evidence from a single adequate and well-controlled clinical 

trial supported by independent evidence, such as data from another 

trial for a treatment of a different type of infection. Also, the 

recommended primary clinical endpoint was redefined as a reduction 

in lesion size of at least 20 percent compared to the lesion size of 

those patients that did not receive treatment at 48 to 72 hours. 24

• FDA made similar changes to its draft 2010 guidance on HABP/VABP 

based, in part, on work resulting from its coordination with both the 

Foundation for the National Institutes of Health and the Clinical Trials 

Transformation Initiative.25 Industry stakeholders expressed concerns 

about this 2010 guidance document that included the agency’s use of 

all-cause mortality (i.e., death from any cause) as the only clinical 

endpoint recommended to measure the effectiveness of a drug. 

Stakeholders also raised concerns about the restrictive inclusion 

criteria that were used to determine which patients could be enrolled 

in clinical trials. In 2014, FDA released a revised draft HABP/VABP 

guidance document that included changes aimed at addressing these 

concerns.26 Specifically, FDA’s recommendations included endpoints 

besides all-cause mortality and modified the criteria for clinical trial 

enrollment. Making the criteria for enrollment less restrictive could 

make it easier to enroll more patients into clinical trials. Enrolling 

patients into clinical trials is a particular challenge noted by most of 

the drug sponsors included in our study.

The GAIN provisions included another requirement for FDA to release a 

draft guidance document on unmet medical need by the end of June 

 24Primary clinical endpoint refers to the measure of the most important question the 

clinical trial is trying to answer.

25Department of Health and Human Services, Food and Drug Administration, Guidance 

for Industry Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial 

Pneumonia: Developing Drugs for Treatment (Draft) (Silver Spring, Md.: November 2010). 

26Department of Health and Human Services, Food and Drug Administration, Guidance 

for Industry Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial 

Pneumonia: Developing Drugs for Treatment (Draft) (Silver Spring, Md.: May 2014). 
Page 13 GAO-17-189 FDA Qualified Infectious Disease Products

2013, and a final version of this guidance by the end of 2014.27 In July 

2013, FDA released its draft guidance—Guidance for Industry 

Antibacterial Therapies for Patients with Unmet Medical Need for the 

Treatment of Serious Bacterial Diseases.28 According to FDA, the agency 

did not meet the statutory deadline for publishing finalized guidance 

because of concerns that release of such guidance could create 

confusion within the industry while Congress considers draft legislation for 

a potential limited population antibacterial drug approval pathway.29 In 

October 2016, FDA told us that the agency intended to release the final 

guidance later that year, once the legislative disposition of this limited 

population approval pathway was clear. However, as of January 2017, 

this guidance document remained in draft form, and FDA had not 

released a finalized version. FDA recently told us that the agency plans to 

release finalized guidance “soon.” 

Although it is too soon to determine if GAIN has actually stimulated the 

development of new antibiotics, FDA has taken steps to implement the 

GAIN provision related to the QIDP designation and the incentives 

associated with the approval of a QIDP drug. Since 2012, FDA has 

granted 101 requests for the designation. Six drugs with the designation 

have been approved, but they were in the later stages of the drug 

development process than the other drugs for which the designation was 

requested when they received this designation.30

FDA data from July 9, 2012, (when the QIDP designation was created) 

through December 31, 2015, showed that FDA granted almost all of the 

 27Pub. L. No. 112-144, § 806, 126 Stat. 1082 (codified at 21 U.S.C. § 355 note)). FDA 

defines unmet medical need as a condition whose treatment or diagnosis is not addressed 

adequately by available therapy. 

28Department of Health and Human Services, Food and Drug Administration, Guidance 

for Industry Antibacterial Therapies for Patients with Unmet Medical Need for the 

Treatment of Serious Bacterial Diseases (Silver Spring, Md.: July 2013).

29See, for example, S. 185, 114th Cong. (as introduced Jan. 16, 2015). On December 13, 

2016, legislation authorizing a limited population pathway for certain antibacterial and 

antifungal drugs became law. See, Pub. L. No. 114-255, § 3042, 130 Stat. 1033, ___ 

(2016).

30According to FDA, the QIDP designation applies to a specific drug product for a specific 

use for which it is being studied. Therefore, one drug may receive more than one QIDP 

designation. From July 2012 through December 2015, there were 56 unique drugs that 

received at least one QIDP designation. 

FDA Used the QIDP 

Designation and Its 

Associated Incentives to 

Encourage the 

Development of Antibiotics
Page 14 GAO-17-189 FDA Qualified Infectious Disease Products

requests that it received for the QIDP designation. Specifically, drug 

sponsors submitted more than 100 requests to FDA for QIDP designation 

during this time, of which FDA granted more than 90 percent.31 (See table 

3.)

Table 3: Number and Percentage of Granted Requests for the Food and Drug 

Administration’s (FDA) Qualified Infectious Disease Products (QIDP) Designation, 

July 9, 2012, through December 31, 2015

Fiscal year Total number of 

requests for QIDP 

designationa

Total number of 

requests for QIDP 

designation granted

Percentage of 

granted requests

2012b 5 5 100

2013 31 26 84

2014 34 33 97

2015 27 25 93

2016c 12 12 100

Total 109 101 93

Source: GAO analysis of FDA data. │ GAO-17-189

Note: Requests that were not granted include those that were denied, were pending a decision, or 

were withdrawn by the drug sponsor. Also, according to FDA, the QIDP designation applies to a 

specific drug product for a specific use for which it is being studied. Therefore, one drug may receive 

more than one QIDP designation. 

a

The number of requests were for antibiotics and did not include requests for other types of products 

not eligible for the QIDP designation, such as biologic license applications. For the purposes of this 

report, we use the term antibiotics to refer to substances that are able to inhibit or kill bacteria to treat 

an infection (i.e., antibacterials). The Generating Antibiotic Incentives Now provisions also refer to 

certain antifungals—substances that are able to inhibit or kill fungi. Thus, we use the term antibiotics 

to refer to both antibacterials and antifungals.

b

Data are from July 9, 2012, through September 30, 2012.

c

Data are for the first quarter of fiscal year 2016 (October 1, 2015, through December 31, 2015).

Drug sponsors whose products received the QIDP designation are also 

eligible to receive fast track designation. From July 2012 through 

December 2015, FDA granted fast track designation to all of the drug 

sponsors whose applications received QIDP designation and also 

 31According to FDA, the number of products with QIDP designation is much larger than 

the number of products that will eventually be submitted in a new drug application. 
Page 15 GAO-17-189 FDA Qualified Infectious Disease Products

requested fast track designation.32 (See table 4.) However, not all drug 

sponsors that requested the QIDP designation also requested fast track 

designation. For example, in fiscal year 2015 (the most recent year for 

which a full year of data are available), FDA granted 25 requests from 

drug sponsors for the QIDP designation, making them also eligible for fast 

track designation. While FDA granted 11 requests from sponsors for fast 

track designation, sponsors could have requested fast track designation 

in 14 additional instances, but they did not do so. According to FDA 

officials, this is likely the case for one of three reasons: (1) a drug sponsor 

has chosen not to request fast track designation, (2) a drug sponsor has 

not yet requested fast track designation but may intend to; or (3) the drug 

sponsor received fast track designation prior to the creation of the QIDP 

designation in 2012, and this is not reflected in the counts.

Table 4: Number of Requests and Requests Granted for the Qualified Infectious Disease Products (QIDP) and Fast Track 

Designations Granted by the Food and Drug Administration (FDA), July 9, 2012, through December 31, 2015

Fiscal year Total number of 

requests for QIDP 

designationa

Total number of 

requests granted 

for QIDP 

designationb

Number of requests 

for fast track 

designation for QIDP 

drugsc

Number of requests 

granted for fast track 

designation for QIDP 

drugs 

Number of eligible 

QIDP drugs for which 

fast track designation 

was not requested

2012d 5 5 4 4 1

2013 31 26 17 17 9

2014 34 33 20 20 13

2015 27 25 11 11 14

2016e 12 12 9 9 3

Total 109 101 61 61 40

Source: GAO analysis of FDA data. │ GAO-17-189

Note: According to FDA, the QIDP designation applies to a specific drug product for a specific use for 

which it is being studied. Therefore, one drug may receive more than one QIDP designation. Also, 

drug sponsors whose applications are granted QIDP designation are also entitled to fast track 

designation. However, according to FDA officials, these numbers might not be equal for one of three 

reasons: (1) a drug sponsor has chosen not to request fast track designation, (2) a drug sponsor has 

not yet requested fast track designation; or (3) the drug sponsor received fast track designation prior 

to the creation of the QIDP designation in 2012 and is not reflected in the counts.

a

The number of requests for designation excludes requests that were submitted for drugs that are not 

eligible for QIDP designation. Requests that were not granted QIDP designation include those that 

were denied, were pending a decision, or were withdrawn by the drug sponsor.

 32Drug sponsors’ applications for QIDP-designated drugs also receive priority review and, 

if approved, may be eligible for market exclusivity. However, priority review is not granted 

until a formal drug application is submitted, and market exclusivity is not determined until 

after the application has been approved. The drugs for which sponsors requested the

QIDP designation and fast track designation during this time might not have progressed 

far enough in the development process to be eligible for these other two incentives. 
Page 16 GAO-17-189 FDA Qualified Infectious Disease Products

b

The number of requests were for antibiotics and did not include requests for other types of products 

not eligible for the QIDP designation, such as biologic license applications. For the purposes of this 

report, we use the term antibiotics to refer to substances that are able to inhibit or kill bacteria to treat 

an infection (antibacterials). The Generating Antibiotic Incentives Now provisions also refer to certain 

antifungals—substances that are able to inhibit or kill fungi. Thus, we use the term antibiotics to refer 

to both antibacterials and antifungals.

c

Applications that received fast track designation prior to July 9, 2012, are not included in these 

counts.

d

Data are from July 9, 2012, through September 30, 2012.

e

Data are for the first quarter of fiscal year 2016 (October 1, 2015, through December 31, 2015).

As of October 2016, FDA had approved applications for six drugs that 

received the QIDP designation for marketing in the United States, though 

these drugs were in the later stages of their development program when 

the designation was created in July 2012. (See table 5.) Four of the six 

approved drug applications also had fast track designation, and all of 

them received priority review. FDA did not grant fast track designation to 

two of these applications because, according to the sponsors, they did 

not apply for it. To date, FDA has determined that five of these six drugs 

are eligible for 5 years of additional market exclusivity because each drug 

were eligible for at least one other type of market exclusivity and the 

statutory requirements for the 5 additional years were met.

Table 5: Food and Drug Administration (FDA) Drugs Approved with the Qualified Infectious Disease Products (QIDP) 

Designation, as of October 2016

Drug name and sponsor Approval date Indication Priority 

review

Fast track 

designation

QIDP 

exclusivitya

Dalvance

(dalbavancin hydrochloride)

Allergan, Inc.

May 23, 2014 Antibacterial to treat acute bacterial 

skin and skin structure infections

Yes Yes Yes

Sivextrob

(tedizolid phosphate)

Merck & Co., Inc.

June 20, 2014 Antibacterial to treat acute bacterial 

skin and skin structure infections

Yes No because 

sponsor did not 

request

Yes

Orbactiv

(oritavancin diphosphate)

The Medicines Company

Aug. 6, 2014 Antibacterial to treat acute bacterial 

skin and skin structure infections 

Yes No because 

sponsor did not 

request

Yes

Zerbaxa (ceftolozane and

tazobactam)

Merck & Co., Inc.

Dec. 19, 2014 Antibacterial to treat complicated 

intra-abdominal infections, in 

combination with metronidazole, and 

complicated urinary tract infections, 

including pyelonephritis

Yes Yes Yes
Page 17 GAO-17-189 FDA Qualified Infectious Disease Products

Drug name and sponsor Approval date Indication Priority 

review

Fast track 

designation

QIDP 

exclusivitya

Avycaz

(ceftazidime and avibactam)

Allergan, Inc.

Feb. 25, 2015 Antibacterial to treat complicated 

intra-abdominal infections in 

combination with metronidazole, and 

complicated urinary tract infections in 

patients who have limited or no 

alternative treatment options, 

including acute pyelonephritis

Yes Yes Pendingc

Cresembab

(isavuconazonium sulfate)

Astellas Pharma U.S., Inc.

Mar. 6, 2015 Antifungal to treat adults with two 

types of invasive fungal infections 

(aspergillosis and invasive 

mucormycosis)

Yes Yes Yes

Source: GAO analysis of FDA data and other information. │ GAO-17-189

a

Dalvance, Sivextro, Orbactiv, and Zerbaxa received new chemical entity exclusivity and QIDP 

exclusivity. Cresemba received new chemical entity, orphan drug, and QIDP exclusivity. As of 

October 2016, the market exclusivity for Avycaz was still pending, according to FDA. New chemical 

entity exclusivity provides 5 years of market exclusivity upon approval if a drug includes an active 

moiety (a certain molecule or ion responsible for the physiological or pharmacological action of the 

drug substance) that has not been previously approved by FDA. Orphan drug exclusivity provides 7 

years of market exclusivity under certain circumstances to drugs designated for treatment of rare 

diseases or conditions. Exclusivity under the Generating Antibiotic Incentives Now provisions adds 5 

years of additional market exclusivity under certain circumstances to drugs with the QIDP designation 

and that are eligible for another type of exclusivity.

b

This drug was approved for two different dosage forms (injection and pill form), involving two 

separate application submissions to FDA.

c

As of October 2016, the market exclusivity for Avycaz was still pending, according to FDA.

Drug Sponsors in Our 

Study Said That GAIN 

Has Facilitated FDA’s 

Review of Their 

Antibiotic 

Applications, but Also 

Expressed Concern 

about Available 

Guidance
Page 18 GAO-17-189 FDA Qualified Infectious Disease Products

All 10 of the drug sponsors in our study said that increased 

communication with FDA or the expedited review of their QIDPdesignated drug applications due to GAIN were beneficial to their drug 

development processes. Five drug sponsors said that the QIDP 

designation was particularly helpful to smaller sponsors. This was 

confirmed by 3 of the smaller drug sponsors in our study that said the 

QIDP designation helped continue their respective development 

programs for antibiotics. Research indicates that as of May 2016, over 80 

percent of the antibiotic products in development were being developed 

by small drug sponsors.33

Eight of the drug sponsors in our study attributed this increase in 

communication with FDA, typically associated with the fast track 

designation, to the agency’s implementation of the GAIN provisions and 

general commitment to supporting the development of new antibiotics. 

For example, 2 of the 10 sponsors specifically noted that they had not 

experienced this level of access to FDA officials during the review of their 

other, non-QIDP-designated drug applications. Five of the 10 sponsors 

said that FDA was receptive to considering new approaches to the design 

of their clinical trials. For example, one drug sponsor stated that FDA 

officials worked with sponsors to find innovative ways to design antibiotic 

clinical trials allowing them to more quickly advance their drugs through 

the development process.

All of the four drug sponsors in our study whose drugs were approved 

with a QIDP designation also received priority review designation, which 

helped to advance their applications more quickly through the FDA review 

process. FDA data showed that these drugs had an average total review 

time of about 8 months, which is consistent with FDA’s priority review 

goal time for new molecular entities.34 Five drug sponsors told us that 

 33The Pew Charitable Trusts, Issue Brief: Tracking the Pipeline of Antibiotics in 

Development, updated May 2016 (Washington, D.C.: 2016). Pew relied on data reported 

by Pharmaceutical Executive in June 2014, which relied on drug sponsor financial 

documents and industry sales surveys. 

34According to FDA, all QIDP drugs approved to date have contained a new molecular 

entity, which is an active ingredient that contains no active moieties that have been 

previously approved by the agency or have been previously marketed as a drug in the 

United States. Active moieties are certain molecules or ions responsible for the 

physiological or pharmacological action of the drug substance. For new molecular entities, 

FDA’s goal is to review and act on a priority review application within 6 months of the 60 

calendar day filing review period that begins on the date of FDA’s receipt of the original 

drug application (a total review time of 8 months). 

All Drug Sponsors in Our 

Study Told Us That 

Increased Communication 

with FDA or the Expedited 

Review of Their 

Applications Were 

Beneficial to Their Drug 

Development Processes
Page 19 GAO-17-189 FDA Qualified Infectious Disease Products

priority review, for which QIDP-designated drugs have automatically 

qualified, was a particularly valuable incentive associated with the QIDP 

designation and GAIN provisions. According to FDA, the agency did not 

typically provide priority review to antibiotic drug applications before the 

GAIN provisions were enacted because these drugs generally do not 

meet the criteria to receive this designation.35

Several of the drug sponsors in our study expressed concern about how 

much they could rely on FDA’s draft guidance documents or the lack of 

guidance describing the QIDP designation and its requirements. FDA 

released half of the guidance documents it revised in accordance with the 

GAIN provisions in draft form, and several of these documents were 

updates to prior draft guidance. Although these guidance documents 

were in draft form, FDA made them publicly available on its website and 

offered them as examples of guidance they had revised to encourage 

antibiotic development in response to GAIN. According to FDA, guidance 

documents represent FDA’s current thinking on a topic and serve as a 

way for the agency to communicate with drug sponsors for the purpose of 

assisting them in developing drugs. However, the FDA draft guidance 

documents on developing antibiotics that we examined indicated on the 

title page and on subsequent pages that they were intended for comment 

purposes only, not for implementation, and would represent the agency’s 

current thinking “when finalized.” Thus, while these draft guidance 

documents can include updated information, it is unclear if the new 

information represents FDA’s current thinking on a topic or if the purpose 

of the draft guidance is limited to generating public comment. Three of the 

10 drug sponsors expressed concern about the role of FDA’s draft 

guidance. For example, a drug sponsor called some of FDA’s guidance 

“dated” and noted that FDA’s guidance documents have remained in draft 

form for a long time. Another drug sponsor said it would rather rely on 

final guidance not directly applicable to its work than on draft guidance 

that was directly applicable. A third drug sponsor noted FDA’s draft unmet 

need guidance was issued in 2013, and said that it would be helpful if 

FDA finalized it.

 35In addition to a QIDP designation, a drug application receives priority review if it is for (1) 

a drug intended to treat a serious condition and, if approved, would provide significant 

improvement in safety or effectiveness; (2) a labeling change resulting from a pediatric 

study; or (3) a drug whose application was submitted with a priority review voucher.

Several of the Drug 

Sponsors in Our Study 

Expressed Concern about 

Available FDA Guidance 

Documents
Page 20 GAO-17-189 FDA Qualified Infectious Disease Products

Further, five sponsors in our study said that elements of the QIDP 

designation were unclear and that written guidance from FDA related to 

the QIDP designation and its incentives would help them to better 

understand the requirements and associated benefits. For example, one 

of these five drug sponsors told us that guidance about the eligibility 

requirements and process for obtaining a fast track designation for 

sponsors’ QIDP-designated drug applications would be helpful. Our 

review of FDA data showed that from July 2012 through December 2015, 

drug sponsors that were eligible for fast track designation because they 

had received QIDP designation for their drug applications could have 

made 40 additional requests for fast track designation, but did not. 

Further, we found that the number of requests for fast track designation 

for eligible QIDP-designated drugs decreased from 20 in fiscal year 2014 

to 11 in fiscal year 2015 (the two most recent years for which a full year of 

data were available). This same drug sponsor told us that the sponsors 

who did not request a fast track designation might have been unsure 

about what information to include in their request or could have been 

unsure if their applications qualified for the designation. These five drug 

sponsors also said that elements associated with the market exclusivity 

incentive for which a QIDP-designated drug application might qualify were 

also unclear. For example, a drug sponsor we spoke with said that 

uncertainty about how FDA was implementing the additional years of 

market exclusivity associated with this designation could affect a drug 

sponsor’s long-term planning for drug development.36

FDA did not provide us with answers to our questions about why some 

QIDP-related guidance documents remain in draft form or whether drug 

sponsors should rely on draft guidance when developing antibiotics, FDA 

officials did agree that guidance related to the QIDP designation might be 

helpful to drug sponsors. FDA officials said the agency frequently 

receives questions about the QIDP designation and application process, 

but did not provide an explanation for why they have not yet developed 

QIDP guidance. They said they consider a range of factors when 

determining which guidance documents to develop, such as new scientific 

developments. Federal internal control standards on information and 

 36Several drug sponsors also told us that the market exclusivity incentive might not 

stimulate the development of new antibiotics because the additional years of market 

exclusivity granted to qualified drugs are unlikely to extend past the typical patent life of a 

new drug. Market exclusivity and patent life generally run concurrently. While market 

exclusivity can range from about 3 to 7 years from drug approval, according to FDA, a 

drug patent generally expires 20 years from the date the patent holder filed its application 

with the United States Patent and Trademark Office. 
Page 21 GAO-17-189 FDA Qualified Infectious Disease Products

communication state that sharing quality information with external parties 

is necessary to achieving an entity’s objectives.37 FDA uses its guidance 

documents to communicate its current thinking on a topic to drug 

sponsors with the purpose of assisting them as they develop new drugs, 

including antibiotics. FDA also implements other expedited programs and 

has developed written guidance that details their features and the criteria 

a drug sponsor must meet to take advantage of them.38 However, a lack 

of clarity on the role of draft guidance documents for and a lack of 

guidance on the QIDP designation could create uncertainty for drug 

sponsors about how much reliance they should place on these draft 

documents and could diminish the likelihood that some drug sponsors 

apply for the designation because they do not fully understand its 

requirements and benefits. As a result, drug sponsors that are working to 

develop new antibiotics could be doing so without the benefit of clear 

current guidance and the likelihood that the QIDP designation will 

encourage the development of new antibiotics may be diminished.

Amid growing concern about antibiotic resistance to existing drugs and a 

steady decline in the number of new antibiotics under development, the 

QIDP designation is a tool for FDA to encourage drug sponsors to 

develop new antibiotics by facilitating the review of applications for these 

drugs prior to their approval. FDA revised guidance documents related to 

antibiotic development in accordance with GAIN, but then released many 

of them in draft form with language suggesting that the guidance is for 

discussion purposes only. Several of the drug sponsors with whom we 

spoke expressed concern about the agency’s use of draft guidance and 

how much reliance they could place upon it. Although FDA has granted 

101 requests for the QIDP designation since being implemented in 2012, 

half of the sponsors that we spoke with said they were unclear about how 

to apply for fast track designation if QIDP designation has been granted 

and about how FDA is interpreting and applying the market exclusivity 

incentive. Moreover, FDA has not produced written guidance that 

describes the requirements and benefits of the QIDP designation. Without 

a clear understanding of the role of draft guidance documents for and the 

requirements and benefits of the QIDP designation, drug sponsors’ 

antibiotic development programs might not be based on FDA’s most 

 37GAO-14-704G.

38Department of Health and Human Services, Food and Drug Administration, Guidance 

for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (Silver 

Spring, Md.: May 2014).

Conclusions
Page 22 GAO-17-189 FDA Qualified Infectious Disease Products

current thinking and sponsors might not take advantage of the 

designation. Therefore, the likelihood that revised guidance on antibiotic 

development and the QIDP designation will encourage the development 

of new antibiotics may be diminished.

In order for drug sponsors to benefit from FDA’s revised guidance on 

antibiotic development and take full advantage of the QIDP designation, 

we recommend that FDA

• clarify how drug sponsors should utilize draft guidance documents 

that were released in accordance with GAIN, and

• develop and make available written guidance on the QIDP 

designation that includes information about the process a drug 

sponsor must undertake to request the fast track designation and how 

the agency is applying the market exclusivity incentive.

We provided a draft of this report to HHS for its review and comment. 

HHS provided written comments, which are reprinted in appendix III. In its 

written comments, HHS agreed to consider our first recommendation and 

to implement our second recommendation. 

With regard to our first recommendation, which calls for FDA to clarify 

how drug sponsors should utilize the draft GAIN guidance documents, 

HHS stated that these documents are provided to enable public comment 

on ideas FDA is considering. HHS noted that they are not binding and 

that drug sponsors can use an alternative approach, if the approach 

satisfies the requirements of applicable statutes. We appreciate FDA’s 

consideration of this recommendation, and firmly believe this clarification 

is warranted. GAIN called for FDA to issue draft guidance documents and 

to review and revise them, as appropriate, to reflect scientific 

developments. FDA’s practice of releasing guidance that remains in draft 

form for years has created uncertainty for drug sponsors in this area. This 

approach leaves sponsors to plan their antibiotic drug development 

programs and determine how to meet statutory requirements without the 

benefit of written guidance representing FDA’s most current thinking. 

Therefore, we believe our recommendation that FDA clarify how drug 

sponsors should use these draft documents is appropriate and wellsupported.

Recommendations for 

Executive Action

Agency Comments

and Our Evaluation
Page 23 GAO-17-189 FDA Qualified Infectious Disease Products

HHS agreed with our second recommendation that FDA develop and 

issue written guidance on the QIDP designation. HHS said that FDA 

intends to proceed promptly with this task and that it will include 

information about the process for requesting the fast track designation 

and the criteria for determining whether an application qualifies for the 5 

additional years of QIDP market exclusivity.

HHS also provided technical comments, which we incorporated as 

appropriate.

As agreed with your offices, unless you publicly announce the contents of 

this report earlier, we plan no further distribution until 30 days from the 

report date. At that time, we will send copies to the appropriate 

congressional committees, the Secretary of HHS, and other interested 

parties. In addition, the report is available at no charge on the GAO 

website at http://www.gao.gov.

If you or your staff have any questions about this report, please contact 

me at (202) 512-7114 or dickenj@gao.gov. Contact points for our Offices 

of Congressional Relations and Public Affairs may be found on the last 

page of this report. GAO staff who made key contributions to this report 

are listed in appendix IV.

John E. Dicken

Director, Health Care
Appendix I: Additional Food and Drug 

Administration (FDA) Antimicrobial Resistance 

Efforts

Page 24 GAO-17-189 FDA Qualified Infectious Disease Products

FDA has other efforts related to antimicrobial resistance beyond the steps 

taken to implement the Generating Antibiotic Incentives Now provisions 

described in this report. The following describes some of the agency’s 

activities outside of the Center for Drug Evaluation and Research and the 

Antibiotic Drug Development Task Force.

According to FDA, the FDA Antimicrobial Resistance Task Force 

comprises principle subject matter experts from across the agency. 

Members include the Center for Drug Evaluation and Research, the 

Center for Biologics Evaluation and Research, and the Center for Devices 

and Radiological Health. According to FDA, this Task Force is intended to 

foster dialogue between the Centers and to ensure that senior staff are 

apprised of major activities and developments related to antimicrobial 

resistance across the agency. In addition to coordinating activities within 

FDA, the Antimicrobial Resistance Task Force coordinates with external 

stakeholders, such as the Biomedical Advanced Research and 

Development Authority on developing a network of sites for clinical trials 

for antibiotics.1 It also serves as the agency’s primary lead on other 

efforts, such as the President’s Combating Antibiotic-Resistant Bacteria 

initiative.2

The Center for Biologics Evaluation and Research within FDA regulates 

biological products for human use, including nontraditional therapies that 

have the potential to be marketed as alternatives to antibiotics. According 

to officials, there are three types of nontraditional therapies under 

development—phage therapy, probiotics, and fecal microbiota.

• Lytic bacteriophage (phage) therapy involves the use of viruses to 

destroy the cell membrane of bacteria. Interest in this type of therapy 

has become relevant, in part, because of the growing global threat of 

antimicrobial resistance. This type of therapy has been reported to 

 1

An entity within the Department of Health and Human Services, the Biomedical 

Advanced Research and Development Authority provides an integrated, systematic 

approach to the development and purchase of necessary vaccines, drugs, therapies, and 

diagnostic tools for public health emergencies. 

2

This initiative is a government-wide effort and addresses the development and 

implementation of actions to detect, prevent, and control illness and death related to 

antibiotic-resistant infections. 

Appendix I: Additional Food and Drug 

Administration (FDA) Antimicrobial 

Resistance Efforts

FDA’s Antimicrobial 

Resistance Task Force

Center for Biologics 

Evaluation and Research
Appendix I: Additional Food and Drug 

Administration (FDA) Antimicrobial Resistance 

Efforts

Page 25 GAO-17-189 FDA Qualified Infectious Disease Products

have been used in Eastern Europe; however, use in the United States 

has only been investigational.

• Probiotics, also referred to as live biotherapeutic products, are 

products that contain live organisms, such as bacteria, that are found

naturally in humans. Proposed uses include the prevention or 

treatment of diarrhea associated with infections by certain bacteria or 

with use of antibiotics.

• Fecal microbiota for transplantation refers to a procedure in which 

fecal matter or bacteria from the stool of healthy individuals are 

administered to a patient to treat a disease. Infection by certain bad 

bacteria can result in debilitating and sometimes fatal diarrhea.

The Center for Devices and Radiological Health is the Center within FDA 

that is responsible for overseeing the safety and effectiveness of medical 

devices sold in the United States, including in vitro diagnostics.3 In vitro 

diagnostics include antimicrobial susceptibility testing devices, which are 

used by laboratories to assess whether a particular bacterium is 

susceptible or resistant to single or multiple antibiotics. These tests are 

based on antibiotic breakpoints, which are the antibiotic concentrations 

used to determine bacterial susceptibility. Officials said they work with the 

Center for Drug Evaluation and Research to jointly publish guidance 

related to antimicrobial susceptibility testing devices.4 According to 

officials, the challenges to the development of antimicrobial susceptibility 

testing devices are mostly scientific. For example, they said it is inherently 

challenging to develop a diagnostic test that quickly and accurately 

identifies if a patient’s symptoms are caused by a bacteria or virus, and 

for bacterial infections, whether the bacterium is resistant to standard 

therapies.

 3

Medical devices include instruments, apparatuses, machines, and implants that are 

intended for use to diagnose a disease or condition, or cure, mitigate, treat, or prevent 

disease, or to affect the structure or any function of the body. See 21 U.S.C. § 321(h).

These devices range from simple tools such as bandages and surgical clamps to 

complicated devices such as pacemakers. 

4

Department of Health and Human Services, Food and Drug Administration, Coordinated 

Development of Antimicrobial Drugs and Antimicrobial Susceptibility Test Devices, Draft 

Guidance for Industry and Food and Drug Administration Staff (Draft) (Silver Spring, Md.: 

September 2016).

Center for Devices and 

Radiological Health
Appendix II: Antibiotic-Related Guidance 

Documents Released by the Food and Drug 

Administration

Page 26 GAO-17-189 FDA Qualified Infectious Disease Products

The guidance documents listed below were released by the Food and 

Drug Administration in relation to the Generating Antibiotic Incentives 

Now statute as of August 2016.

Department of Health and Human Services. Food and Drug 

Administration. Bacterial Vaginosis: Developing Drugs for Treatment 

Guidance for Industry (Draft). Silver Spring, Md.: 2016. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM510948.pdf

Department of Health and Human Services. Food and Drug 

Administration. Vulvovaginal Candidiasis: Developing Drugs for 

Treatment Guidance for Industry (Draft). Silver Spring, Md.: 2016. 

http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugsgen/documents/document/ucm509411.pdf

Department of Health and Human Services. Food and Drug 

Administration. Anthrax: Developing Drugs for Prophylaxis of Inhalational 

Anthrax Guidance for Industry (Draft). Silver Spring, Md.: 2016. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM070986.pdf

Department of Health and Human Services. Food and Drug 

Administration. Uncomplicated Gonorrhea: Developing Drugs for 

Treatment Guidance for Industry. Silver Spring, Md.: 2015. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM401620.pdf.

Department of Health and Human Services. Food and Drug 

Administration. Complicated Urinary Tract Infections: Developing Drugs 

for Treatment Guidance for Industry. Silver Spring, Md.: 2015. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM070981.pdf.

Department of Health and Human Services. Food and Drug 

Administration. Complicated Intra-Abdominal Infections: Developing 

Drugs for Treatment Guidance for Industry. Silver Spring, Md.: 2015. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM321390.pdf.

Appendix II: Antibiotic-Related Guidance 

Documents Released by the Food and Drug 

Administration
Appendix II: Antibiotic-Related Guidance 

Documents Released by the Food and Drug 

Administration

Page 27 GAO-17-189 FDA Qualified Infectious Disease Products

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Hospital-Acquired Bacterial 

Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing 

Drugs for Treatment (Draft). Silver Spring, Md.: 2014. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM234907.pdf.

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Community-Acquired Bacterial 

Pneumonia: Developing Drugs for Treatment. Silver Spring, Md.: 2014. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM123686.pdf.

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Pulmonary Tuberculosis: 

Developing Drugs for Treatment (Draft). Silver Spring, Md.: 2013. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM373580.pdf.

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Acute Bacterial Skin and Skin 

Structure Infections: Developing Drugs for Treatment. Silver Spring, Md.: 

2013. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/ucm071185.pdf

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Antibacterial Therapies for Patients 

with Unmet Medical Need for the Treatment of Serious Bacterial Diseases 

(Draft). Silver Spring, Md.: 2013. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM359184.pdf.

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Acute Bacterial Sinusitis: 

Developing Drugs for Treatment. Silver Spring, Md.: 2012. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM070939.pdf
Appendix II: Antibiotic-Related Guidance 

Documents Released by the Food and Drug 

Administration

Page 28 GAO-17-189 FDA Qualified Infectious Disease Products

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Acute Bacterial Exacerbations of 

Chronic Bronchitis in Patients with Chronic Obstructive Pulmonary 

Disease: Developing Antimicrobial Drugs for Treatment. Silver Spring, 

Md.: 2012. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM070935.pdf

Department of Health and Human Services. Food and Drug 

Administration. Guidance for Industry Acute Bacterial Otitis Media: 

Developing Drugs for Treatment. Silver Spring, Md.: 2012. 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfo

rmation/Guidances/UCM070947.pdf
Appendix III: Comments from the Department 

of Health & Human Services

Page 29 GAO-17-189 FDA Qualified Infectious Disease Products

Appendix III: Comments from the 

Department of Health & Human Services
Appendix III: Comments from the Department 

of Health & Human Services

Page 30 GAO-17-189 FDA Qualified Infectious Disease Products
Appendix IV: GAO Contact and Staff 

Acknowledgments

Page 31 GAO-17-189 FDA Qualified Infectious Disease Products

John E. Dicken, (202) 512-7114 or dickenj@gao.gov

In addition to the contact named above, Tom Conahan, Assistant 

Director; Gay Hee Lee, Analyst-in-Charge; George Bogart; Laurie 

Pachter; Sarah M. Sheehan; and Katherine A. Singh made key 

contributions to this report.

Appendix IV: GAO Contact and Staff 

Acknowledgments

GAO Contact

Staff 

Acknowledgments

(100505)
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