approved, OOPD is interested in determining the status of the remaining 1,525 orphans that have not yet received approval. While some are probably in development, others have been abandoned for various scientific or business reasons, and it is likely that some of these designees still hold promise. OOPD plans to develop criteria that could be used to screen the regulatory submissions for the remaining designated orphans to determine which hold promise.

Explore the possibility of orphan policy in drug review. There is no special policy for the review of drugs to treat rare diseases; prior to approval, all drugs are required to have shown “substantial evidence of effectiveness” (21 CFR §314.50). And while the FDA review divisions have, according to Coté, sense, sensibility, and sensitivity with regard to the issues surrounding orphan drugs, the level of understanding is not homogeneous. FDA would like to consider what if any policies might be needed to better facilitate the review of orphan drugs and is beginning discussions to that end internally and with Institute of Medicine (IOM) leadership.

Mentor the review divisions in the fundamental science underlying small clinical trials. In 2001, the IOM released a report on conducting and interpreting small clinical trials (IOM, 2001). Expanding on this study, OOPD would like to establish a curriculum to enhance the knowledge of reviewers regarding the fundamental science underlying small clinical trials. As highlighted in the IOM report, there are new methodologies, each with its own strengths and weaknesses, with which reviewers should be familiar. OOPD hopes to create a cadre of go-to reviewers who would have expertise in small clinical trials and interpretation of the data that orphan drug sponsors would submit, and would employ these new methodologies.

Act globally. OOPD has worked to establish relationships with regulatory agencies around the world, particularly EMEA. Globally, there are patients with the same diseases and researchers working to understand the same underlying science. EMEA passed its own orphan drug act in 1999, and while there are some important differences, the EMEA and U.S. acts have many similarities. EMEA and FDA now share a joint application form for orphan product designation that can be submitted to either or both EMEA and FDA. The processes are still independent, but the agencies hold monthly teleconferences and are reviewing many of the same applications. There is also an exchange program whereby people from the European orphan drug office and OOPD meet to learn how each operates. Coté noted that OOPD has not yet reached out significantly to Japan and other countries, but that such interactions are planned for the future.



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