FDA is Advancing the Goals of the Orphan Drug Act

By: Scott Gottlieb, M.D.

Three months ago, I committed to fully eliminate a backlog of about 200 orphan drug designation requests that were pending review with FDA, and to implement policies that would require FDA to respond to all new designation requests within 90 days of receiving them. Moreover, the agency pledged to never allow a backlog of these designations to accumulate again.

Dr. Scott GottliebAt that same time, I said that we may pursue other policies that we believe would enable us to better advance the goals of the Orphan Drug Act (ODA). All of these commitments were part of a new Orphan Drug Modernization Plan that we announced on June 29th.

I’m pleased to update you on our progress in meeting each of these objectives.

First, owing to the dedicated efforts of the orphan drug designation team who oversee the Orphan Drug Designation Program, the first of these goals has been fully achieved. Reviews of all orphan drug designation requests older than 120 days were completed on August 28th. This was well ahead of the September 21st deadline that we had set for ourselves under our orphan drug plan. The achievement is hopeful news for those with a rare disease, defined as a disease which generally affects fewer than 200,000 people in the United States. Companies that receive orphan drug designation for their product qualify for various incentives including tax credits for clinical trial costs, relief from prescription drug user fees and the potential for seven years of marketing exclusivity after the drug is approved.


Orphan Drug Designation Requests By Year

Orphan Drug Designation Requests By Year

Note: Designations granted in a given year may include requests received from that year as well as previous years.


Second, we’re putting in place new policies to improve the efficiency of our review process to ensure that we meet our new 90-day mandate to prevent new backlogs.

Finally, we’re going to be taking new policy steps to make sure that the incentives offered by the ODA are granted by FDA in a way that’s consistent with the manner Congress intended. To that end, FDA will soon hold a public meeting to get input on complex scientific and regulatory issues such as those raised by molecularly targeted drugs and biologics and the appropriate application of orphan incentives in that paradigm. As part of this process, FDA will also be examining aspects of how the agency grants designations, to make sure they continue to reflect current science and drug development and the goals intended by Congress.

For all the success of the ODA, there’s been criticism that some sponsors are using designations as a way to sidestep other important public health goals set out by Congress. We need to make sure our policies take notice of all of these new challenges and opportunities.

FDA plans to advance certain guidance documents and other policies to address these issues. One guidance document will close a loophole that allows sponsors to avoid an obligation to study drugs in pediatric indications. This circumstance arises if sponsors received an orphan designation for a pediatric subtype of an otherwise common and non-orphaned adult disease.

The longstanding practice of allowing pediatric subpopulations of common diseases to be designated as orphan conditions was intended to promote pediatric drug development. It pre-dated the implementation of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act (PREA), two laws that were specifically aimed at promoting more pediatric studies.

Now, instead of instigating more pediatric research, the granting of the orphan designation in the pediatric subpopulation can have the opposite effect. It can allow sponsors to sidestep pediatric study requirements that are part of other laws aimed at promoting this same research.

Consider a condition like inflammatory bowel disease. A drug may be approved to treat the large population of adults with the condition. Then the same drug may be granted an orphan designation to treat the much smaller population of a subset of children suffering from the same condition.

But once a drug receives an orphan designation for a pediatric population of the adult disease, the drug then becomes statutorily exempt from the requirements of PREA. This occurs even in cases where the sponsor never goes on to develop the drug for this pediatric use. These PREA requirements could have required the sponsor to study the drug for this or other uses in children. By granting the drug a pediatric orphan designation, it means the drug never has to actually be studied for a pediatric use. It’s a loophole that is in direct opposition to what Congress intended.

Nobody envisioned this unintended conflict between the original ODA and the provisions outlined in PREA. In effect, by letting sponsors designate pediatric subpopulations of drugs intended to treat adult diseases, the drug makers receive an unintended “free pass” from having to study drugs in these or other pediatric uses. Thus, rather than ensuring more pediatric research, as Congress envisioned, we can end up with fewer pediatric studies. FDA will soon issue a draft guidance document that’s aimed at closing this inadvertent loophole.

Taking these and other steps to modernize our stewardship of the ODA is imperative. Science is giving us new opportunities to use the tools offered by the ODA to advance innovation in more areas of medicine where patients have few, if any options. At the same time, the demands on FDA’s orphan drug program continue to grow. We need to make sure the policies governing how we implement these key provisions are modern and efficient.

The number of requests received by FDA under the Orphan Drug Designation Program has steadily increased over the past five years, rising to 568 new requests in 2016. This is more than double the number of requests received in 2012.  Patients with rare disease often have limited or no treatment options. We want to maximize new opportunities for patients.

FDA will continue to make full use of tools provided by Congress to apply incentives for the efficient development of rare disease therapies, and for activating more pediatric research. These steps will help us achieve our ultimate goal: to facilitate the development of safe, effective innovations that have the potential to meaningfully impact rare diseases.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA takes step to encourage pediatric drug studies

By: Lynne Yao, M.D. 

We all know that children are not just small adults. Many changes occur in children as they grow and develop that can affect how a drug works. In fact, some drugs that work in adults may not work at all in children. There may be different safety concerns compared to when they are used by adults, or they may need to be given in a different dose. That’s why products that are used in children must be studied in children. 

Congress enacted two laws that will increase the study of drugs in children: The Best Pharmaceuticals for Children Act (BPCA) provides an incentive for drug companies to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity. The Pediatric Research Equity Act (PREA) requires drug companies to study their products in children under certain circumstances. When pediatric studies are required, they must be conducted with the same drug and for the same use for which they were approved in adults. 

Before BPCA and PREA became law, more than 80% of the drugs approved for adult use were being used in children, even though the safety and effectiveness had not been established in children. Today that number has been reduced to about 50%. 

Under PREA, FDA can waive studies in children if the studies are not necessary. For example, if the disease for which the drug is being used in adults does not exist in children, such as prostate cancer, FDA would waive studies for children. In some cases, FDA has allowed sponsors to defer pediatric studies, depending on the circumstances. However, deadlines for deferred studies have often been missed. 

Fortunately, FDA now has tools to discourage companies from missing deadlines for deferred pediatric studies. When Congress reauthorized PREA last year as part of the Food and Drug Administration Safety and Innovation Act, or FDASIA, it gave FDA new authorities. FDA can grant extensions for deferred pediatric studies at a sponsor’s request if there is good cause for a delay in completing the studies. For example, if the sponsor has diligently attempted to recruit patients, but is having difficulty recruiting enough pediatric patients to complete the study, FDA can grant a deferral extension. However, if a sponsor has failed to seek or obtain a deferral extension, has failed to submit deferred pediatric studies by the final due date agreed to with FDA, or has failed to request approval for a required pediatric formulation, FDA can send a non-compliance letter to the sponsor and publish the letters on the web. 

This week, FDA is publishing the first of these non-compliance letters and the sponsors’ responses. They will be posted to a public FDA web page on an ongoing basis. We believe this important step demonstrates our ongoing commitment to getting these studies done for the benefit of all infants and children. 

Lynne Yao, M.D., is Associate Director, Pediatric and Maternal Health Staff, in FDA’s Center for Drug Evaluation and Research’s Office of New Drugs