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This past June, the FDA released its Orphan Drug Modernization Plan designed to shorten the time required to secure an orphan disease drug designation. The agency identified its desire to clear the backlog of nearly 200 products awaiting approval for an orphan designation by September 21 and provide an avenue to expedite approval process. The agency recently announced progress against clearing the backlog, eliminating all submissions older than 120 days. It further unveiled initiatives to streamline the process and to assess the incentives for orphan drug development to align to the original intent of the Orphan Drug Act. These promising developments continue to reinforce the potential impact of the agency’s approach to ensure the orphan designation maximizes value for patients and minimizes loopholes exploited by manufacturers that stifle clinical development.

On September 12, FDA Commissioner Gottlieb announced the agency successfully cleared the backlog and did it ahead of schedule; by August 28, they had cleared all requests older than 120 days.  We initially had concerns the agency might lessen its standards in exchange for a quick turnaround. While the progress is meaningful, we do not know exactly how each evaluation was conducted or to what level the standards were upheld. This is a point that warrants continued observation as recently designated products seek regulatory approval.

Commissioner Gottlieb’s next steps further indicate the FDA is taking the right approach to the moderation plans; reiterating its goal to establish a 90-day mandate for the review process to prevent future backlogs. Commissioner Gottlieb detailed the agency’s plan to pursue a range of process improvements to ensure it meets this lofty goal. From a pure process standpoint, these are positive indications the FDA takes this approach seriously and will apply the right methodologies to increase the efficiency of the process. All aspects of its approach should identify improvements that provide benefit to manufacturers seeking approval and hold the agency accountable:

  • Realign staff across medical product centers to drive workload efficiencies and better utilize expertise
  • Apply lean management principles to build a new process map, optimized to reduce delay
  • Develop new metrics for measuring success

In line with the existing push for transparency, we would also recommend additional efforts to be made by the agency to provide increased visibility into the applications backlog and decisions. This will ensure accountability for achieving their approval turnaround goals and to maintaining standards in approvals.

The more encouraging aspect is how the FDA plans to approach the approval guidelines and incentives into the future. At a future public meeting, it will seek input on “complex scientific and regulatory issues such as those raised by molecularity targeted drugs and biologics and the appropriate application of orphan incentives in that paradigm.”1 Based on this external input and other internal assessments, the FDA will review how the approval committees grant orphan designations and put forth policies and guidance documents to better align incentive to driving patient outcomes.

The initial focus is to close a loophole allowing life sciences companies to not conduct pediatric studies for the orphan designated products, normally a mandate based on the Pediatric Research Equity Act (PREA). While the PREA is designed to promote pediatric drug development, an orphan designation for a pediatric subpopulation means a study can be avoided. This conflict of interest ends up working counter to the original intent of PREA – to drive more pediatric trials.

Why does that matter? It shows the FDA is serious about taking a systematic and thorough approach to ensuring the right products get an orphan designation and the true benefits of the designation do not detract from the scientific requirements for drug development. Life sciences companies may incur a cost and time penalty from these additional studies, but the overall benefit to the patient community, especially the pediatric one, will be immense.

The FDA is making the right moves and saying the right things. If the trend continues, more orphan drug designations will be granted and it will be up to the FDA to ensure the right approvals are given in such an efficient way that both life sciences companies and patients can benefit.