the production runs; generators must be prepared; the Tc-99m must be eluted; radiopharmaceuticals must be prepared and tested; all of this information must be compiled; and the sNDA must be written and submitted.
The committee received presentations from industry and the FDA (see Appendix C) concerning the time, cost, and uncertainties for regulatory approvals. Perhaps the most striking aspect of the presentations was the vast difference in what industry representatives expected from the FDA—a complex, tedious, expensive, and unpredictable process—and the simple, straightforward, and readily achievable approval process described by the FDA presenter.
Industry representatives provided the committee with several examples of the difficulties they have encountered in obtaining FDA approvals for new sources of Mo-99. These included a “difficult” process for obtaining approval for a backup supplier of Mo-99 who used the same production and processing protocols in an already-approved NDA (it was reported to the committee that approval took almost a year and cost more than $200,000), and another approval that took almost 2 years. A representative of CORAR suggested that the FDA could require clinical trials before it would approve the use of LEU-based Mo-99.
The FDA presenter told the committee that the review time for an NDA typically takes between 6 and 10 months. He also noted that engaging the FDA early during the process of developing the NDA can help ensure that the approval process runs smoothly. A consultant working for MURR who has long experience with the FDA approval process estimated it would take a minimum of about 4–6 months after submission of the necessary paperwork and cost about $84,000 to obtain approval for using Mo-99 from a new LEU-based process at the MURR reactor (MURR, 2006). A current Mo-99 producer told the committee that not all FDA approvals require long lead times. This producer obtained emergency approval of a backup Mo-99 supply in less than a week.
Technetium generator producers are well acquainted with the FDA approval process and have a good understanding of its requirements. If LEU-based Mo-99 can be produced with similar chemical characteristics similar to HEU-based Mo-99—and current experience in Argentina and Australia indicates that it can—it is hard for the committee to see any rational basis for expectations of substantial delays in FDA approvals if producers submit high-quality sNDAs and work with FDA staff throughout the approval process. It is especially difficult for the committee to see how the FDA would ever require clinical trials as part of an sNDA for a new Mo-99 source. Mo-99 is a well-known isotope that can be produced with low impurities using either an HEU- or LEU-based process. Clinical trials would be a useless exercise in any case because they can be used to detect only gross adverse drug effects.