1. FDA Science BoardNov 5, 20041 CDER Risk-based Site Selection Model: An FDA Risk Management Tool Presentation to FDA Science Board November 5, 2004 by Kara Morgan, Ph.D., Office of Planning/Office of the Commissioner

2. FDA Science BoardNov 5, 20042 Upgrading FDA Risk Management Tools FDA is interested in formalizing risk management tools Rigorous, science-based methods are available Commissioner’s Strategic Plan – Efficient Risk Management Difficult to evaluate efficiency when risk management tools are not formalized OMB Oversight Transparency, Consistency, Accuracy Risk as a meaningful public health metric

3. FDA Science BoardNov 5, 20043 Motivation for the CDER Risk-based Site Selection Model Previous (pre FY05) approach CDER identified “high-risk” as sterile drugs, Rx drugs, new registrants, exclude medical gas ORA decided where to go within those categories Problems Insufficient resources to inspect all sites “High-risk” category wasn’t discriminating enough CDER wanted to incorporate additional information Solution: a formal model to rank sites by risk Note: Before the use of the model, decisions were risk-based but not formalized. Risk-related knowledge was incorporated by the field.

4. FDA Science BoardNov 5, 20044 Process for Model Development Working group established under CGMP: CDER, CBER, CVM, ORA and OC Defined risk; brainstormed risk factors Risk = harm to patient from low quality product Categorized factors into three bins: product- related, process-related, facility-related Evaluated available data for assessing these factors Developed weights for the factors

5. FDA Science BoardNov 5, 20045 Product-related Factors Intrinsic factors Sterility Prescription Recall data By product class Includes measure of severity

6. FDA Science BoardNov 5, 20046 Facility-related Factors History Time elapsed since last inspection Compliance and Violation record Estimated production volume Establishment type (i.e., manufacture, repacking, relabeling, testing, sterilizing) Source of data: FACTS (Field Accomplishments and Compliance Tracking System)

7. FDA Science BoardNov 5, 20047 Process-related Factors Inherent Process Risk Factors, including potential for contamination Process Controls and Risk Mitigating Factors No data available An expert elicitation was conducted to assess potential for risk by process Modeled after an expert elicitation by ISPE

8. FDA Science BoardNov 5, 20048 Combining the factors Weights for each factor/subfactor Empirically derived Expert judgment as needed Algorithm developed to combine weights and factors Output: a Site Risk Potential (SRP) Score for each facility A higher score means more potential for risk

9. FDA Science BoardNov 5, 20049 A Plain Language Summary of the Influence of the Factors A site will be less frequently selected for inspection if… It has been inspected recently and has few or no previous violations of GMPs and a smaller volume of product (facility weight) It make non-sterile, OTC drugs, and/or other product types that are not associated with a high frequency of recalls and for serious defects (product weight) It makes products judged to be relatively straightforward to manufacture with consistent quality, and not vulnerable to contamination (process weight)

10. FDA Science BoardNov 5, 200410 Implementation in FY05 Model was run for all active sites in FACTS A list was generated for each District, with the Site Risk Potential Score reported for each site. The basis for the score in terms of the rating on product factor, facility factor, and process factor was reported The field were asked to use the list of ranked sites to prioritize their inspections.

11. FDA Science BoardNov 5, 200411 Next steps Continuous Improvement Provide incentives for better data, including the addition of more factors Feedback from ORA on utilization of rankings Sensitivity Analysis of factors and weights Evaluation underway by Office of Planning CVM considering use for prioritization of animal drug inspections

12. FDA Science BoardNov 5, 200412 Expected Outcomes Better predictability for industry Incentives for risk mitigation activities Increased (measurable!) efficiency and effectiveness in terms of resource use Higher product quality Improved public health