There is an expectation to select the worst case molecules based on criteria such as Toxicity, Potency, Cleanability etc. However, this may be mis-implemented at times to select worst case molecules based on each criteria independently. This is certainly against the Risk-based approach where Risk needs to be assess as a function of Severity (Toxicity, Potency), Probability (Solubility or Cleanability) and Detectability (VRL, Method).
Moving to an integrated Risk-Assessment is not only accurate and scientific but also leads to fewer worst case molecules and significantly reduces the probability of Analytical Method Failure.