Why is the acceptable daily dose significantly less than the therapeutic dose?
As defined in ISPE's Baseline Guide: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP), the term acceptable daily exposure (ADE) is defined as:
"The daily dose a substance below which no adverse events are anticipated, by any route, even if exposure occurs for a lifetime."
It's important to note that ADEs are designed to protect the general population from unintentional cross-contamination of one product into another product by any route of potential exposure; and that this "general population" may include sensitive subpopulations such as the very young (new-borns) to the very old (the elderly) with impaired organs/smaller body weight AND that they could be exposed to a cross-contaminated product for every day of their life.
As such, ADE values will always be significantly lower than therapeutic dose levels (since all drugs have some effects at therapeutic levels (some may be beneficial/some adverse, but in either case would be unintentional if due to a cross-product contamination issue).
Once the ADE value is derived, it is not used directly, but then is inserted in the maximum safe carryover equation to derive the residue on the swab level.
Sources: Walsh, A. (2011). Cleaning Validation for the 21st Century: Acceptance Limits for Active Pharmaceutical Ingredients (APIs): Part II