Comment from Ryan DeSalvo

1. Introduction: I am an independent consultant in the Pharmaceutical industry who has participated in FDA Drug CGMP Inspections and responded to FDA Form 483 observations. I focus primarily on root cause analysis and addressing deviations. 2. Background: This comment pertains to “Responding to FDA Form 483 Observations at the Conclusion of a Drug CGMP Inspection: Draft Guidance for Industry.” Specifically Section IV, part C, lines 305 - 307 (page 10) which state: “A risk assessment helps establishments identify and understand the potential effect an observation has on patient safety, manufactured drugs (whether or not they have been distributed), and future drug quality.” 3. Analysis This paragraph is situated in the section for developing an investigation plan and conducting an investigation. The paragraph itself has no actionable statements or recommendations to perform or modify a risk assessment. The preceding section - Section IV, part A, “Understanding and Assessing the Observations” explicitly states (Lines 232 - 235) “During and immediately after the close of an inspection, an establishment’s management should fully understand all observations and assess any related risks to product quality and patient safety. Establishments should take timely and appropriate actions based on this risk assessment.” During an investigation conducted per Section IV, Part C, an establishment is likely to identify new information that may modify the findings of the risk assessment that was performed as recommended in Section IV, Part A (Lines 232 - 235). The example provided in lines 309 - 314 illustrate this concept. If and when a firm identifies such new information, the risk assessment performed for Section IV, Part A should be updated to assess the newly identified information. The text of Section IV, Part C should be updated to explicitly recommend an updated risk assessment based on the findings of the investigation as stated in this comment, or similarly phrased. 4. Recommendations The identified text of Section IV Part C should be updated to read as follows, or similarly: “A risk assessment helps establishments identify and understand the potential effect an observation has on patient safety, manufactured drugs (whether or not they have been distributed), and future drug quality. During and after the comprehensive investigation of an observation and its causes, any newly identified relevant information should be assessed for risk to patient safety, manufactured drugs, and future drug quality.”