Positron Emission Tomography drugs, or PET drugs (not to be confused with drugs approved for companion animals), would be accorded more equitable user fee status under PDUFA IV if the Senate-passed version of the FDA Revitalization Act (“FDARA”) is signed into law. (A similar provision is included in the House version of PDUFA IV, H.R. 2900, introduced late last month.) FDARA, if enacted, would also address an issue raised by The Council on Radionuclides and Radiopharmaceuticals (“CORAR”) in an August 2005 citizen petition, in which the organization requested that “FDA establish a class waiver under which manufacturers of PET drugs are exempt from multiple establishment user fees, and are subject, at most, to a single establishment fee for each approved ‘human drug application.’”
The FDC Act defines the term “compounded positron emission tomography drug” at § 201(ii) to mean a drug that “(A) exhibits spontaneous disintegration of unstable nuclei by the emission of positrons and is used for the purpose of providing dual photon positron emission tomographic diagnostic images; and (B) has been compounded by or on the order of a practitioner who is licensed by a State to compound or order compounding for a drug described in subparagraph (A), and is compounded in accordance with that State’s law, for a patient or for research, teaching, or quality control.” The term includes “any nonradioactive reagent, reagent kit, ingredient, nuclide generator, accelerator, target material, electronic synthesizer, or other apparatus or computer program to be used in the preparation of such a drug.”
A more practical description is provided in the CORAR petition:
PET drugs are produced by tagging (i.e., “labeling”) a substrate compound with a positron emitting isotope, which is produced in cyclotrons (i.e., devices that accelerate protons or deuterons to the high energies needed for a nuclear reaction to occur). Once injected, the isotope travels through a patient’s bloodstream and is distributed in certain tissues. Using a PET camera, nuclear physicians measure the different rates at which the isotope emits positrons, based, for example, on the different ways in which different types of tissue metabolize the drug’s substrate, and thereby produce computerized images of biochemical processes and tissue structures within the body. Physicians use the resulting images to diagnose, stage, and monitor diseases (e.g., focal epilepsy, certain cardiac diseases, dementias, and lung, breast, prostate, and colorectal cancer).
The FDA Modernization Act of 1997 placed a moratorium on FDA’s regulation of PET products as “new drugs” until the Agency establishes procedures by which PET drugs are to be approved under the FDC Act’s new drug approval process, and establishes appropriate PET drug current Good Manufacturing Practices (“cGMPs”). During this moratorium, FDA has encouraged PET centers to voluntarily submit marketing applications for approval, and issued proposed regulations in September 2005 to establish PET drug cGMPs.
CORAR has been concerned that, because of the unique characteristics and properties of PET drugs, FDA will assess multiple establishment user fees for each approved PET drug. The CORAR petition states that:
Because of the unusual characteristics of PET drugs, and once all PET drugs are regulated as “new drugs,” the assessment of establishment user fees, in particular, will significantly and unfairly burden commercial PET drug manufacturers. Due to the short half-lives of PET drugs, a commercial manufacturer that supplies PET drugs nationally, or even regionally, requires multiple manufacturing establishments located throughout the U.S. or the region (as the case may be). Each of these establishments must be identified in any marketing application submitted to FDA. Because establishment fees are assessed annually for “each prescription drug [manufacturing] establishment listed in [an] approved human drug application,” PET drug applicants would be assessed multiple establishment fees. Such multiple fee assessments would be patently unfair, particularly for an industry that will soon be saddled with numerous new and expensive legal and regulatory burdens.
At a recent public meeting on PDUFA IV, CORAR provided the following example: “[O]ne PET drug manufacturer operates 44 cyclotron facilities nationwide. If these were used to manufacturer and supply a particular PET drug under an NDA, this company would have to pay over $13 million annually in establishment fees (based on FY 2007 user fee rates).”
FDARA would amend FDC Act § 736(a) to create special establishment user fee rules for PET drugs. Under the Senate-passed version of FDARA:
[E]ach person who is named as the applicant in an approved human drug application for a compounded [PET] drug shall be subject . . . to one-fifth of an annual establishment fee with respect to each such establishment identified in the application as producing compounded [PET] drugs under the approved application.
FDARA would also exempt from all annual establishment user fees those PET drug sponsors who certify to FDA that they are not-for-profit medical centers with only a single PET drug manufacturing establishment, and provided at least 95% percent of the total number of doses of each PET drug produced by that establishment will be used within the medical center itself.
Although FDARA does not place all PET drug sponsors on equal footing with therapeutic drug sponsors (in the example above, the PET drug sponsor would still have to pay the equivalent of almost 6 full establishment fees for its 44 establishments), it would, if enacted, provide significant relief for multi-establishment PET producers.