Under the now-established guidelines, if a PET drug used in a clinical trial is being made at a facility for which manufacturing data have been submitted in an NDA or ANDA, the FDA will not object to use of the PET drug in a clinical trial without an IND until December 12, 2015.
"However, if significant manufacturing deficiencies are found during the NDA or ANDA review, or during inspection of the facility the PET drug is sourced from, the FDA may notify the sponsor that the PET drug may no longer be used in clinical trials," the communiqué stated.
The Food Safety Modernization Act directs the FDA to establish appropriate approval procedures and current good manufacturing practice (cGMP) requirements for PET drugs and specifies that PET drug manufacturers and compounders be required to submit applications for approval within 24 months of their procedures and requirements.
The FDA's initiative dates back to December 2009, when the agency issued a final rule on cGMPs for all PET radiopharmaceuticals, requiring companies and facilities to submit NDAs or ANDAs for their products. The rule covered all PET drug producers, including those affiliated with hospitals and academic medical centers, as well as unaffiliated regional manufacturers.
The final rule stipulated that PET drug manufacturers submit applications by December 12, 2011. However, until June 12, 2012, the FDA had no plans to take enforcement actions against a facility making PET drugs for clinical use if the facility had not submitted an NDA by December 12, 2011, as long as the manufacturer was in compliance with all other FDA statutes, including cGMP guidelines.
With this week's declaration, the FDA is mandating that PET drug producers operate under an approved NDA or ANDA or effective IND by December 12, 2015.
In the document, the FDA noted it might be very difficult to develop NDAs for certain PET drugs that are currently in clinical use, but the guidelines specify that expanded access is available for these types of drugs.
According to the FDA, as of September 1, 2011, there were 12 PET drugs that had U.S. Pharmacopeial Convention (USP) monographs:
- N-13 ammonia injection
- C-11 methionine injection
- C-11 carbon monoxide
- C-11 raclopride injection
- F-18 FDG injection
- Rb-82 rubidium chloride injection
- F-18 fluorodopa injection
- C-11 sodium acetate injection
- C-11 flumazenil injection
- F-18 sodium fluoride injection
- C-11 mespiperone injection
- O-15 water injection
Of the 12 drugs with a USP monograph, N-13 ammonia, F-18 FDG, F-18 sodium fluoride, and Rb-82 rubidium chloride have been approved by the FDA for production at certain facilities.
USP provides pending monographs for certain drug products, drug substances, and excipients that have been submitted or are intended to be submitted to the FDA for marketing clearance in the U.S.