FDA’s Flexibility in the Approval of Orphan Drugs

Abstract

We wish to thank Mr Sasinowski for his comprehensive review of orphan drug approvals within the US noncancer setting. We greatly appreciate his documentation of the regulatory flexibility and scientific judgment that FDA has exercised in the service of patients with rare diseases. The agency similarly recognizes the important contributions that the rare disease community has made to our shared mission in public health, and the timely review and approval of orphan drugs has been an FDA priority. Of the 30 new molecular entities that the agency shepherded through review and approval last year, more than one-third were indicated for rare diseases. We have recently completed our own analysis of orphan drug approvals issued for oncologic as well as nononcologic indications between 2006 and February 2012, by the FDA Center for Drug Evaluation and Research. The results of our analysis speak to the FDA product review programs that Mr Sasinowski frames in terms of regulatory flexibility. In this time period, there were 104 orphan drug approvals, approximately two-thirds of which relied on approval programs that allow for deviation from the traditional standard criterion for clinical evidence based on 2 or more adequate and well-controlled trials. In agreement with Mr Sasinowski’s analysis, we concur that individual orphan drug development programs are often unique, with their own particular biomedical exigencies, and we have accordingly seen considerable diversity among the clinical trial designs that were used to support the orphan drug approvals that we examined (2006–2012). Trial design as manifested in these approvals is highly dependent on the characteristics of the disease, drug, and population under study. Other factors have also contributed to the regulatory flexibility that we have seen in orphan drug development. For example, we believe that an especially important basis for achievements in orphan drug development was the establishment of close and thoughtful communication between regulatory agencies and drug developers. The timely review and approval of orphan drugs remains an FDA priority. From our own assessment of drug approvals for rare diseases, we would stress the importance of the collaborative dimensions of the process, involving FDA staff, trial investigators and sponsors, as well patients and members of the rare disease community. We urge orphan drug developers to work closely with the FDA throughout drug development—especially early on in the process—so that clinical evidence can be efficiently and appropriately assessed in terms of US statutory standards for approval. The sharing of information and perspectives among the various stakeholders of drug development has clearly increased in recent years and will likely remain crucial, not only for the approval of new drugs to treat rare diseases but also to meet needs that are more broadly emerging in the current health care setting.