The drug manufacturer’s application is required to  include such items as a description of the rare disease, documentation of  the number of people affected by the disease in the United States (the  population estimate), and a scientific rationale explaining why the drug  may effectively treat the disease. FDA’s Marketing Approval Process

FDA’s marketing approval process is the same for all drugs, regardless of  orphan status. FDA Implemented Its Modernization Plan to Address Growing Demand for Orphan Designations, and Has Recently Met Timeliness Goals

In June 2017, FDA issued its Orphan Drug Modernization Plan and has  implemented a number of steps under the plan to address the demand for  orphan designations. 3.) As of March 2018, FDA  officials reported that OOPD management has received these tracking  reports on a daily basis, which identify the number of days that have  elapsed for each application pending review, among other things. FDA Uses Consistent Criteria to Grant Orphan Designation, but Reviews Do Not Include Complete Information

		FDA Generally Applies Consistent Criteria in Reviewing Applications for Orphan Designation, but Did Not Ensure that All Required Information was Appropriately Recorded or Used

OOPD applies two consistent criteria (i.e., two particular criteria that all  designation applications must meet) when determining whether to grant a  drug orphan status: (1) the disease that the drug is intended to treat  affects fewer than 200,000 people in the United States, and (2) there is  adequate scientific rationale that the drug may effectively treat the  disease. In addition, our analysis of 148 OOPD review templates completed for  new designation applications received from October to December 2017  provided further detail on OOPD’s designation determinations since  implementing its Orphan Drug Modernization Plan. According to FDA officials, although the background information required  in the review template may not directly affect a designation decision, it  provides important context that is critical to ensuring a complete review of  a designation application. 5.) FDA review time. 7.) FDA has also conducted studies to understand rare disease drug  development challenges. Stakeholders and Research Identified Ongoing Rare Disease Drug Development Challenges, while Opinions on the Orphan Drug Act Incentives Varied

Stakeholders we interviewed, including industry experts and patient  advocacy groups, and research we reviewed identified general rare  disease drug development challenges, as well as more specific concerns  pertaining to the ODA incentives and pricing. The two barriers to rare  disease drug development most commonly cited among stakeholders we  interviewed were (1) the need for more basic scientific research (e.g.,  understanding patient experiences and progression of symptoms, known  as a disease’s natural history), and (2) the difficulty in recruiting small  populations for clinical trials. In contrast, many patient advocacy groups we spoke with noted that  drug manufacturers’ ability to obtain ODA incentives under certain  circumstances, such as multiple orphan designations for the same drug,  are needed for further investment in drug development. However, we found that FDA does not always ensure that  all information is consistently recorded in its review templates and  evaluated when making designation determinations, which are critical  steps needed to understand the full context of a drug’s intended use in  the rare disease. In its written comments, reproduced in  appendix III, the agency concurred with our recommendation. Appendix I: Information Recorded in OOPD’s Standard Designation Review Template

In October 2017, the Food and Drug Administration’s Office of Orphan  Products Development (OOPD) introduced a standard review template,  along with guidance for how to complete it, to aid its reviewers in  evaluating orphan designation applications.
Why GAO Did This Study

The ODA provides incentives, including tax credits and exclusive marketing rights, for manufacturers to develop drugs to treat rare diseases, which are typically defined as affecting fewer than 200,000 people in the United States. Approximately 7,000 rare diseases affect an estimated 30 million people in the United States, and only 5 percent of rare diseases have FDA-approved treatments.
GAO was asked to examine FDA's orphan drug processes. In this report, GAO examines, among other things, (1) the actions FDA has taken to address the growing demand for orphan designations; (2) the extent to which FDA has used consistent criteria and complete information in reviewing orphan designation applications; and (3) the steps FDA has taken to address rare disease drug development challenges. GAO analyzed FDA documents and data, as well as all designation review templates FDA completed as of March 2018 for applications received from October to December 2017. GAO interviewed agency officials, as well as stakeholders, including drug manufacturers, industry experts, and patient advocacy groups.

What GAO Found

The Food and Drug Administration's (FDA) Office of Orphan Products Development is responsible for reviewing drug manufacturer applications for orphan designation. Drugs granted this designation treat rare diseases and may receive various incentives under the Orphan Drug Act (ODA). As the number of orphan designation applications received and granted has grown, FDA outlined several process changes in its June 2017 modernization plan to improve designation review timeliness and consistency.
In evaluating designation applications, FDA reviewers generally apply two consistent criteria—(1) the size of the rare disease population, and (2) the scientific rationale that the drug may effectively treat the disease. To inform their evaluation, reviewers must record certain background information in a standard review template, such as the drug's U.S. marketing history. Officials told us this information provides important context, such as whether FDA has experience with a little known disease, critical to ensuring a complete designation application review. However, GAO's analysis of 148 designation review templates found that FDA does not consistently record or evaluate background information when making designation decisions. For example, 48 of 148 review templates GAO analyzed were missing information on the drug's U.S. marketing history. As such, FDA cannot be sure that reviewers are conducting complete evaluations that include all critical information needed for assessing its criteria.
Stakeholders GAO interviewed and research GAO reviewed identified a number of rare disease drug development challenges, such as the difficulty in recruiting small populations for clinical trials, with differing opinions about the ODA incentives. For example, several stakeholders were critical of manufacturers obtaining multiple orphan designations—and ODA incentives—for the same drug when the drug may otherwise be profitable from treating multiple patient groups. However, many patient advocacy groups noted that granting ODA incentives in these circumstances is needed to encourage drug manufacturers to study the safety and efficacy of drugs in rare disease populations.

What GAO Recommends

FDA should ensure that all required information for reviews of orphan designation applications is consistently recorded and evaluated. The agency concurred with our recommendation.