December 24, 2002
FDA REVISES DEFINITION OF THE TERM “NO RESIDUE”
FDA has published a final rule that revises the definition of “no residue” in the new animal drug regulations to mean that no residue is detected with an approved regulatory method. This means that any residue in the target tissue must be non-detectable or below the limit of detection (LOD) of the approved regulatory method. Under the regulation, FDA has defined the LOD of an analytical method as the lowest concentration of analyte (the chemical that is detected and measured by the analytical method) that can be confirmed by the approved regulatory method. FDA published this final rule in the December 23, 2002, Federal Register.
FDA promulgated “Regulation of Carcinogenic Compounds Used in Food-Producing Animals” on December 31, 1987 (Title 21, Parts 500.80 – 500.92 of the Code of Federal Regulations.) In the regulation, informally referred to as the Sensitivity of the Method (SOM) regulation, FDA provided an operational definition of “no residue” and identified the steps a sponsor of a carcinogenic compound should follow to secure approval of the compound. The regulation implemented the “DES proviso” of the Delaney Clause to the Federal Food, Drug, and Cosmetic Act, which permits the approval of a new animal drug which induces cancer if “no residue” will be found, by methods prescribed or approved by the Secretary, in edible tissues of treated animals.
FDA is revising this definition in response to a 1995 legal opinion issued by the Department of Justice (DOJ), Office of Legal Counsel, which concluded that this operational definition of “no residue” is not legally supportable. However, the DOJ stated that FDA may use the “no significant risk” level as a benchmark for rejecting analytical methods.
Many other key aspects of the regulation (21 CFR 500.80-500.92 -- ) remain the same: the “no significant risk” level will still be determined according to established procedures; the concentration of marker residue that the regulatory method must be capable of measuring in the target tissue (Rm) will still be calculated; the method will still be validated to at least Rm; but, FDA will use submitted data on the method to determine the LOD. Consequently, the data necessary to meet the requirements of the new rule are identical, or nearly identical, to those previously delineated. Moreover, the revision of the definition of “no residue” preserves the same level of public health protection.
This final rule is effective January 22, 2003. Additional information on the final rule may be found in the December 23, 2002 , Federal Register and from:
