Automation and applications of the tolerance limit method in estimating meat withdrawal periods for veterinary drugs

Abstract A program was written in R to facilitate the implementation of the tolerance limit method (TLM) for establishing regulatory withdrawal times for limiting drug residues in meat, milk, and eggs. The developed computer source code can use pharmacokinetic and regulatory data to calculate the drug withdrawal period according to United States Food and Drug Administration (U.S. FDA) guidelines. The code called the “Withdrawal Time Calculator (WTC)” applied this TLM method to meat samples. The program was tested with the data provided by the U.S. FDA guidance and other published data collected from in vivo studies. Additional algorithm validation data were flunixin and sulfamethazine liver concentration data from peer-reviewed publications generated by our laboratory. This manuscript reports the withdrawal period results from testing the developed WTC code. Moreover, the source code for the WTC contains a data removal algorithm, constructed according to U.S. FDA data elimination recommendations if the user chooses. The power of the WTC is that it bypasses the use of multiple platforms typically required to perform the TLM, including standard commercial spreadsheet software (i.e., Microsoft Excel) and Statistical Analysis System (SAS) while providing speed and usability. This novel program provides a platform to calculate a withdrawal period recommendation for any drug in any class of animal for various regulatory body standards and could be very helpful in cases of extra-label drug use in food animals.