We recently reported that 2015 resulted in the highest level of newly approved U.S. drugs in nineteen years. This reflects an industry-wide desire to research and develop drugs for rare and hard-to-treat diseases. As has been reported, while speaking at a recent meeting in Washington, D.C., the U.S. Food and Drug Administration's Director of the Center for Drug Evaluation and Research (CDER), Janet Woodcock, noted the agency has moved to address the backlog of abbreviated new drug applications (NDA). Woodcock added that CDER is working to prepare for the emerging biosimilars market. Additionally, John Jenkins, Director of the Office of New Drugs at CDER, outlined drug approval statistics, particularly as CDER has seen a steep rise in orphan drug approvals.
CDER in 2016
In 2016, Woodcock stressed the need to fill vacancies at the agency's drug offices as of critical importance. CDER will also be engaged in the re-negotiations of the generic drug, prescription drug, and biosimilar user fee programs—the programs expire in 2017, adding to FDA's focus. Other areas of focus for CDER include issuing draft guidance on generic versions of abuse-deterrent opioid formulations, streamline clinical trial monitoring and data cleaning practices, develop and standardize electronic submissions to CDER, and reevaluation of drug advertising and promotion regulations in light of recent court decisions.
Woodcock's comments on promotional activity come as it has been reported in 2015 the Office of Prescription Drug Promotion (OPDP) issued a record-low nine letters to companies for advertising and promotion violations. Four of the letters involved inadequate or omitted risk information and other common citations involved unsubstantiated or misleading statements. FDA has still not finalized its guidance on social media, although the agency has issued several guidances that deal with the issue.
As FDA grapples with staffing concerns and regulatory developments, Congress continues to debate the 21st Century Cures legislation. It easily passed the House, but for months has been stuck in the Senate. Now, news comes that the Senate Health, Education, Labor and Pensions (HELP) Committee will not take up the bill as it marks up legislation on neurological diseases research and electronic medical records. The measure has stalled in the Senate, mostly because Republicans and Democrats have failed to agree on how to pay for the bill. The House bill included more than $8 billion in new funding for researchers at agencies like the National Institutes of Health and provisions seeking to overhaul the FDA.
According to Sen. Lamar Alexander (R-Tenn.): "Senators and staff on our committee have been working together throughout 2015 to produce a number of bipartisan pieces of legislation that are ready for the full committee to consider". "The House has completed its work on the 21st Century Cures Act. The president has announced his support for a precision medicine initiative and a cancer 'moonshot.' It is urgent that the Senate finish its work and turn into law these ideas that will help virtually every American," he said.
GAO: FDA Lacks Reliable and Accessible Postmarket Data
When there is an unmet need for the treatment of a serious condition, FDA may use one or more of its expedited programs, such as fast track and breakthrough therapy designation, which are intended to bring drugs to market more quickly. FDA is also responsible for monitoring the safety of drugs and reporting on those efforts.
With this in mind, the GAO was tasked with providing information about FDA's expedited programs and its postmarket monitoring of expedited and nonexpedited drugs. The report examined (1) the number and types of requests for fast track or breakthrough therapy designation, (2) the number and types of FDA-approved drug applications that used an expedited program, and (3) the extent to which FDA's data on tracked safety issues and postmarket studies allowed the agency to meet its reporting and oversight responsibilities.
The GAO looked at FDA data on requests for fast track or breakthrough therapy designation and approved drug applications that used an expedited program from October 1, 2006, to December 31, 2014. It also reviewed FDA information on tracked safety issues and postmarket studies, including FDA internal evaluations and guidance, and interviewed FDA officials. In its findings, the GAO recommends the FDA develop plans to correct problems with its postmarket safety data and ensure that these data can be easily used for oversight. HHS agreed with GAO's recommendations, according to the report.
Rep. Rosa DeLauro (D-CT), who commissioned the GAO report, said in a statement: "The GAO report confirms my greatest fear, that FDA lacks fundamental resources and leadership in ensuring that drugs brought quickly to market are truly safe and effective." She added: "If FDA is shifting more of the safety risk to consumers by allowing fewer and shorter clinical trials on expedited drugs, adequate tracking of drug safety issues and review of post market studies are absolutely vital."
The GAO's report was especially critical of FDA's CDER office. According to the report, FDA lacks reliable, readily accessible data on tracked safety issues and postmarket studies needed to meet certain postmarket safety reporting responsibilities and to conduct systematic oversight. CDER's internal evaluations of data in its database revealed problems with the completeness, timeliness, and accuracy of the data. These problems have prevented FDA from publishing some required postmarket safety reports in a timely manner, and have restricted its ability to perform systematic oversight.
CDER's data on tracked issues was not complete, indicating that 144 issues had not been formally entered into its database. The time consuming nature of data entry was cited by FDA as a potential reason. GAO reports FDA officials acknowledged that staff were not following CDER's policies and procedures for tracking and documenting potential safety issues, but said that given the high workload of its review staff it had prioritized identifying, assessing, and addressing potential safety issues over administrative tracking. CDER's information on postmarket study status was found to be outdated and inaccurate, also related to staff delays in reviewing submissions.
Additionally, tracked safety issue and postmarket study data were not readily accessible to the GAO for analysis. FDA officials told the GAO much of the information has to be manually reviewed and cannot be accessed electronically. FDA reported to GAO that some information about postmarket studies, such as the date FDA requested or required a study, must be manually collected from the text of letters to sponsors; these letters are not automatically linked to information about the study in internal systems, which can make them challenging to locate.
GAO concludes the FDA's lack of reliable and accessible postmarket safety data prevents the agency from publishing required reports in a timely manner and restricts the FDA's ability to conduct effective oversight. As of October 2015, GAO notes that FDA had not published required annual reports containing data on postmarket studies for fiscal years 2013 and 2014. FDA officials told GAO that the agency had decided to delay publication of the reports primarily due to CDER's internal evaluation of the postmarket study data and subsequent efforts to address the data problems that were identified.
However, to its credit, GAO reported that FDA has taken some steps to address the problems identified with the postmarket safety data, although the agency is not currently announcing any comprehensive plans with goals and time frames. FDA said it intends to address its incomplete data on tracked safety issues by revising and streamlining its processes for reviewing and tracking these issues. FDA officials said that CDER has formed a workgroup that is considering options to clarify which potential safety issues should be centrally tracked, and how the tracking and review processes could be streamlined. Additionally, FDA intends to increase the timeliness and accuracy of its postmarket study data by improving tools for oversight and data collection. FDA officials said the agency is aiming to facilitate more timely review of sponsor submissions that contain information on postmarket studies by improving internal oversight.