This is a great question. Let me start by providing a bit of historical context.
Most industries that are regulated have a history of past environmental or health problems that precipitated the need for governmental oversight in the first place. In the case of crops improved by biotechnology, the regulations were put in place well before any such crops were commercialized, with the express purpose of ensuring that this promising technology would not cause problems. The scientific community began thinking though any potential health or environmental issues starting with a major conference in 1975 (21 years before the first biotech crop was commercially planted).
Working with the broader community of academic and commercial scientists, three US regulatory agencies hammered out a system of shared responsibility for the review of biotech crops. Called the Coordinated Framework for Regulation of Biotechnology, the system was instituted in 1986―still 10 years before the first commercial acre was planted. The proactive involvement of three regulatory agencies is completely unprecedented and has made crops improved through genetic engineering the most carefully monitored foods in history.
The USDA considers whether there are any “plant pest” issues with the specific crop and trait, such as the ability to cross with weedy relatives. The new crop cannot even be planted outdoors for testing purposes until the USDA determines that it is prudent to do so. The EPA gets involved if there is anything pesticide-related to do with the trait, such as tolerance to a herbicide or the production of the Bt protein that protects the plant from insect damage. The FDA reviews the information that the producing company or other entity generates to show that the modified crop is “substantially equivalent” to the non-modified version. This step is technically voluntary, but that sort of data has been provided and reviewed for every biotech trait that has been commercialized in the United States. The exact nature of the equivalency testing is, logically, customized based on the type of trait involved.
This extraordinary review process has probably contributed to the fact that there have been no health or environmental problems associated with biotech crops even though they have been planted on billions of acres over 16-plus years. Opponents of biotechnology frequently say that these crops are untested and unregulated. Nothing could be further from the truth.