A Practical Approach, Second Edition=Ronald D. Ho.pdf

PRINCIPLES OF RISK ASSESSMENT — FDA PERSPECTIVE 8971. Availability of studies?YesNo“Unknown” or “Not Evaluable” RiskInformation is Not Available toAssess Risk2. Relevance of Studies(Test System and Route)No“Unknown” or “Not Evaluable” RiskDefine Non-Relevance of Test Systemor Study(Do Not Use Figure 22.3)Yes3. Presence of a Signalfor an Endpoint?No“No Observed Effect”Use Figure 22.2 for Integration of Datafor Endpoints with No SignalYes“Positive Effect Observed”Use Figure 22.3 for Integration of Datafor Endpoints with Positive ResultsFigure 22.1Overall decision tree for evaluation of reproductive/developmental toxicities.a. Availability of StudiesIf adequate studies were not done or the results are not available for comprehensive evaluation,risk to humans is considered unknown or not possible to evaluate, and the product labeling shouldreflect that conclusion. If studies were conducted and are available for comprehensive evaluation,the assessment should continue.b. Relevance of StudiesIf the test system was not relevant (e.g., nonrelevant route of administration) or not appropriate(e.g., inappropriate test protocol or species), the risk to humans is considered unknown or notamenable to evaluation, and the product labeling should reflect that conclusion. If the studies arerelevant to evaluating the risk to humans, the risk integration process should continue with the nextquestion.c. Presence or Absence of a SignalIf the test system is relevant and appropriate for assessing the risk of toxicity in humans, the nextquestion that should be asked is: “Was there a positive signal (suggesting toxicity)?” If no positivesignal (suggesting toxicity) was seen, the evaluation process should continue to Section B. If apositive signal was seen, the evaluation process should continue to Section C.© 2006 by Taylor & Francis Group, LLC