By Karla L. Palmer –
As announced in the Federal Register on June 3, 2015, FDA is proposing to deschedule [123I]Ioflupane (ioflupane) from Schedule II of the Controlled Substances Act (CSA). Ioflupane is an active pharmaceutical ingredient and new molecular entity in DaTscan, which is a single-dose injectable radiopharmaceutical diagnostic tool used in hospital settings in certain brain imaging studies. Descheduling means that the product will no longer be subject to the requirements of the CSA, its implementing regulations and DEA’s jurisdiction. For example, the registration, handling, recordkeeping and reporting requirements will no longer apply to entities that handle this product. FDA approved an NDA for DaTscan on January 14, 2011 for visualizing certain dopamine transporters (DAT) in the brains of adult patients with suspected Parkinsonian syndromes by using single photon emission computed tomography (SPECT) brain imaging. By definition, ioflupane is (and was from the outset prior to FDA’s approval) a Schedule II controlled substance because it is derived from cocaine (via ecgonine). Each vial of DaTscan contains 0.325 micrograms of ioflupane per 2.5 milliters. DaTscan itself presents “no practical possibility of abuse, misuse, diversion or clandestine production.”
Back in November of 2010 (prior to FDA’s January 2011 approval of DaTscan) HHS recommended to DEA that FDA-approved products containing ioflupane be decontrolled. As required under the Federal scheduling process, as part of its recommendation, HHS provided DEA with a scientific and medical evaluation, which contained an 8-factor analysis setting forth HHS’s reasons for its decision pursuant to 21 U.S.C. § 811(b). DaTscan was used as the basis for the HHS’s medical and scientific evaluation and for DEA’s 2015 8-factor analysis as DaTscan is the only approved diagnostic product containing the ioflupane. DEA’s Notice reviews the 8 factors that DEA must consider when making a scheduling recommendation. The factors all demonstrate that use of the product (generally because of dosing, complexity of cocaine and ecgonine extraction, and radioactive properties) does not create a potential for abuse, dependency, safety or health hazard.
It remains troubling that DEA is just now publishing its Notice of proposal to decontrol this product when both HHS’s and DEA’s analysis showed no evidence of abuse even back in November 2010. DEA indicated that some questions had been directed back to FDA in September 2014, but even then this was still four years after HHS had transmitted its recommendation to DEA and more than three years since the product had been approved for marketing. So, one must question why DEA’s required 8-factor analysis and publication of the Notice comes almost five years after FDA’s approval of DaTscan and HHS’s submission of its scientific and medical recommendation to DEA that DaTscan/ioflupane not be controlled. The delay also raises a bigger concern; specifically, the delay in the descheduling process likely will force companies, as in this case, to market the product under an unwarranted scheduling classification. Put another way, how could a company afford to wait more than four years after approval before marketing the product?
The pending Regulatory Transparency Act (H.R. 639) which passed the House of Representatives in March of this year - see our previous post here - would provide some relief in that it would require that, if the FDA recommends the new drug be scheduled as a II, III, IV, or V substance, the DEA must issue an interim final rule scheduling the drug no later than 90 days following receipt of the FDA’s recommendation. The rule would become immediately effective as an interim final rule. Because ioflupane was already scheduled as a CII in the first instance because is contained a derivative of cocaine, the legislation as drafted would not require DEA to hasten the turtle-like pace of its review of HHS’s medical and scientific evaluations. But this case illustrates again the need for more accountability and implementation of reasonable time periods on Agency decisions affecting access to important medicines.