The 10-ppm criterion for the acceptable concentration of potential API in cleaning validation to minimize cross contamination into to next product has been employed for many years. It is, however, arbitrary and does not take into account advances in toxicological risk-assessment methodologies that allow for robust and scientifically supportable approaches to establish safe or acceptable levels of a drug from one product to the next. Recent guidelines issued by the International Society of Pharmaceutical Engineers in 2010 and the European Medicines Agency in 2014 employ health-based risk assessments as the basis for establishing acceptable limits of residual APIs into the next product manufactured and most importantly are protective for patient safety. This article describes why the 10-ppm criterion, which was established based on analytical limitations and estimates of acceptability, is no longer necessary and why a riskbased approach should be universally adopted.