Orphan Report: The GAO’s Report on Orphan Drug Designations and Approvals

While riding out the end of this term, the Government Accountability Office (GAO) delivered to our lame duck Congress some light reading on orphan drug designations and marketing. In a report titled “FDA Could Improve Designation Review Consistency; Rare Disease Drug Development Challenges Continue,” the GAO examined the orphan drug designation process, including the increase in demand for orphan drug designations and FDA’s review of orphan drug designation requests. Arising in response to a congressional request on orphan designations and marketing approvals, the report examines:

• The actions FDA has taken to address the growing demand for orphan designations;
• The extent to which FDA has used consistent criteria and complete information to review applications for orphan designation, and the characteristics of drugs seeking orphan designation;
• The orphan drugs FDA has approved for marketing; and
• The steps FDA has taken to address challenges in rare disease drug development.

The GAO reviewed FDA documents, data, and review templates for orphan drug designation requests from October to December 2017 and interviewed agency officials and stakeholders.

The GAO investigation and Report come on the heels of FDA’s June 2017 Orphan Drug Modernization Plan designed to eliminate the designation application backlog. As part of the plan, FDA introduced collaboration between different review divisions, reduced other regulatory and discretionary burdens on Office of Orphan Products Development (OOPD) (like FOIA requests), and developed the standard designation template to facilitate consistent and efficient review of new designation applications.

The major focus of the GAO Report seems to be the OOPD review templates. The report explains that OOPD reviewers record information from orphan drug designation requests in a five-section review template, which is then used to assess the request. The GAO noted that of the 148 review templates assessed, at least 102 were missing information. FDA officials explained that the background information in the review template provides context for making designation determinations, but there are no instructions provided to reviewers for using this information in evaluating the applications. Further, the GAO report indicated that OOPD did not independently verify data to ensure accuracy and completeness in designation requests.

While the GAO Report seems fairly critical of the OOPD review process, the Report offered only one recommendation: FDA should improve the consistency of the information inputted into its review templates. (Those of you who have had the pleasure of reviewing FDA’s Summary Basis of Approval in any depth know that a lack of consistency in FDA review templates is not limited to OOPD.) While the recommendation focuses specifically on the templates for some reason, the Report points out some big holes in FDA’s orphan drug designation review process in its entirety. A lack of instructions combined with a lack of data verification implies that OOPD is not doing a thorough review of these designation requests.

The report also noted that concerns with the adequacy of a manufacturer’s scientific rationale was the most common reason that orphan designation was not granted. Concerns include that the manufacturer did not provide sufficient or adequate data to support the scientific rationale, or that the manufacturer did not provide data from the strongest available model for testing the drug. Some other interesting facts from the report: FDA’s orphan drug marketing approvals increased from 2008 to 2017, focused primarily on therapeutic areas of oncology and hematology, and took approximately 9 months for agency review.

FDA approved 77 orphan drugs for marketing in 2017. But as the number of orphan designation and marketing approvals has grown, questions about potential challenges in drug development have arisen. The GAO Report cites as the biggest barriers to rare disease drug development the need for more basic scientific research and difficult recruiting small populations for clinical trials. And while the report explained that OOPD has some grant programs that may help manufacturers, it provided no recommendations or analyses for FDA on this issue.

However, HP&M’s James E. Valentine and Frank J. Sasinowski previously co-authored a proposal for an FDA Rare Disease Center of Excellence that would help overcome these barriers and others in orphan drug development and review (see previous coverage here).