RELATIONSHIP BETWEEN SAFETY DATA AND BIOCONTAINMENT DESIGN IN THE ENVIRONMENTAL ASSESSMENT OF FERMENTATION ORGANISMS - AN FDA PERSPECTIVE

The Center for Veterinary Medicine requires strain/construct-specific data for recombinant fermentation organisms used in the production of animal drugs and feed additives. Fermentation plant biocontainment sch emes are chosen based, in part, upon the ability of the organism to su rvive and persist in the environment and to transfer genetic informati on to indigenous organisms. Survival and persistence study methods may include one of the following ecosystems: activated sludge, mammalian gut, soil or river water. Gene transfer protocols can be incorporated into a persistence study. These studies are designed to show that the recombinant construct behaves similarly to the host in a representativ e ecosystem where the organism could be introduced inadvertently. The studies need to provide repeatable results and reflect current state-o f-art design and methods. Data verification is conducted by FDA invest igators during Good Laboratory Practice inspections. Biocontainment gu idelines, such as those developed by the NIH Recombinant DNA Advisory Committee, set general biocontainment goals for large groupings of rec ombinant organisms. The FDA, as required under the National Environmen tal Policy Act, must base its decision making on verifiable scientific data specific to each application. Therefore, in addition to using th ese guidelines as benchmarks, sponsors are required to submit strain/c onstruct-specific data to support the selection of an appropriate bioc ontainment level. Once additional well-controlled studies for a variet y of constructs are available, broader generalizations as to biocontai nment may be drawn.