FDA oversees the drug development process and the approval of new  drugs for marketing in the United States. 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. 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. 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

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. 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. FDA recently told us that the agency plans to  release finalized guidance “soon.”

		FDA Used the QIDP Designation and Its Associated Incentives to Encourage the Development of Antibiotics

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. FDA data from July 9, 2012, (when the QIDP designation was created)  through December 31, 2015, showed that FDA granted almost all of the  requests that it received for the QIDP designation. Drug Sponsors in Our Study Said That GAIN Has Facilitated FDA’s Review of Their Antibiotic Applications, but Also Expressed Concern about Available Guidance

		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

All 10 of the drug sponsors in our study said that increased  communication with FDA or the expedited review of their QIDP- designated drug applications due to GAIN were beneficial to their drug  development processes. 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. Several of the Drug Sponsors in Our Study Expressed Concern about Available FDA Guidance Documents

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. 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. 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. Federal internal control standards on information and communication state that sharing quality information with external parties  is necessary to achieving an entity’s objectives. 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. Recommendations for Executive Action

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. In its  written comments, HHS agreed to consider our first recommendation and  to implement our second recommendation. GAIN called for FDA to issue draft guidance documents and  to review and revise them, as appropriate, to reflect scientific  developments. Department of Health and Human Services. Food and Drug  Administration. Food and Drug  Administration.
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 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.

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.