Since 1938, the food provisions of FDCA have been amended on a number of occasions, primarily with regard to safety issues. Enforcement strategies for food safety have been built on the premarket approval concept imposed on drugs in the 1938 Act; these strategies place the burden of proof of safety on the manufacturers of new food and color additives. Statutes that modified FDCA include the Pesticides Amendment of 1954 (P.L. 83–518), the Food Additives Amendment of 1958 (P.L. 85–929), the Color Additive Amendments of 1960 (P.L. 86–618), and the Animal Drugs Amendments of 1968 (P.L. 90–399).

Prior to passage of NLEA, Congress expressly provided for preemption of State food labeling regulation under the Fair Packaging and Labeling Act of 1966 (FPLA; P.L. 89–755). FPLA required that the net weight of a food product, as well as other required information, be accurately stated in a uniform location on the label to facilitate value comparisons. FPLA specifically declared that it is the express intent of Congress to supersede any and all laws of the States or political subdivisions thereof insofar as they may now or hereafter provide for the labeling of the net quantity of contents of the package of any consumer commodity covered by FPLA which are less stringent than or require information different from the requirements of Section 4 of the Act or regulation promulgated pursuant thereto (FPLA Section 12 [1461]). This Act also authorized FDA to adopt regulations to prevent the nonfunctional slack fill of packages containing foods. To date, however, FDA has not proposed or promulgated regulations to implement FPLA provisions.

Congress amended FDCA in the Regulatory Amendments of 1948 (P.L. 80–766), expanding its jurisdiction to include any action with respect to a food that results in the article becoming adulterated or misbranded after shipment in interstate commerce. However, there was no attention to national uniformity in the 1938 Act or the 1948 amendment.

Poultry remained subject to FDA regulation until 1957. Passage of the Poultry Product Inspection Act in 1957 (P.L. 85–172) provided USDA with statutory authority for mandatory post-mortem inspection of every carcass and ante-mortem inspection of poultry in interstate commerce, with the Federal government required to pay the cost of the inspection program. The Processed Products Inspection Improvement Act of 1986 (P.L. 99–641) made a basic alteration in the law, to permit less than continuous inspection of processed products (as opposed to fresh meat and poultry); it did not, however, alter the requirement for prior label approval.

Not until 1967 was interest focused on the quality of State inspection of meat and poultry slaughter and processing plants engaged only in intrastate