The U.S. Food and Drug Administration (FDA) on December 10 issued its final rule on current good manufacturing practices (cGMPs) for all PET radiopharmaceuticals, noting that the regulations may have a "significant impact on a substantial number" of small manufacturers.
The final rule sets into motion a two-year timeline during which the FDA will require manufacturers of PET drugs to submit new drug applications (NDAs) or abbreviated new drug applications (ANDAs) for their products. The rule covers all PET drug producers, including those affiliated with hospitals and academic medical centers, as well as unaffiliated regional manufacturers.
The new rule goes into effect on December 12, 2011.
"Like the regulations for conventional drugs, the intent of these new cGMP regulations for PET products is to ensure that PET drugs meet FDA requirements for identity, strength, quality, and purity," said Jane Axelrad, associate director for policy in the FDA's Center for Drug Evaluation and Research (CDER), during a conference call to outline the new rules.
cGMP differences
The agency has noted that PET drugs pose special issues with regard to production and distribution due to their use of radioactive material with short half-lives. Due to PET's roots as a research tool, PET radiopharmaceuticals were not a regulatory priority for the agency.
That began to change in the mid-1990s, however, as PET began to be increasingly used in the clinical setting, and in 1997 the FDA Modernization Act directed the agency to establish approval procedures and cGMP requirements for PET drugs.
The final rule contains several differences between cGMP requirements for PET drugs and regulations for other drugs. Among the differences:
- Allowance for multiple operations (or storage) in the same areas, as long as organization and other controls are adequate
- Self-verification of significant steps in PET drug production
- Same-person oversight of production, review of batch records, and authorization of product release
- Greater flexibility in approaches to determining whether PET drug products conform to specifications
- Simplified labeling requirements
The FDA soon will publish a follow-up guidance document on how PET drug producers can prepare for and submit new drug applications or abbreviated new drug applications.
The agency estimated that the final rule would affect 51 PET drug producers among the 101 facilities that currently manufacture PET drugs in the U.S. According to the FDA, 15 producers own or operate 65 commercial operations, 16 of which are associated with academic hospitals.
Economic impact
Small PET drug producers may feel the greatest impact of the final rule. "At most," the FDA wrote, "a single PET drug producer may incur one-time and annual costs of approximately $57,900 and $32,400, respectively, per production facility."
The agency anticipates that hospital and regional commercial producers will incur higher facility costs, because they "are expected to have to higher noncompliance rates with the written procedure and recordkeeping requirements."
The FDA noted that most of the large corporate PET drug producers and hospitals associated with corporate entities already have complied "to a great degree" with the final rule.
Until the rule becomes effective in December 2011, the FDA will continue to use current standards to inspect PET drug manufacturing facilities. "We have been conducting inspections of PET facilities, even as we have been developing current GMP requirements, and those are the standards we have been applying in those inspections," Axelrad said.
The full version of the FDA's final rule is available in the December 10 issue of the Federal Register (Vol. 74:236, pp. 65412-65436).
By Wayne Forrest
AuntMinnie.com staff writer
December 11, 2009
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