1. Sterile Drug Products Dr. Peter Cooney Associate Director for Microbiology Office of New Drug Chemistry Center for Drug Evaluation and Research

2. Microbiological Risk Potential for Introduction of Microorganism Ability to Proliferate Time/Temperature of Storage

3. Relatively Low-Risk Use of commercially available presterilized components Few and basic aseptic manipulations Closed Systems

4. Relatively High-Risk Intermediate or Open Systems Complex, numerous, or lengthy aseptic manipulations Nonsterile drug substances or components used in preparation

5. Sterility is built into a product through production processes and controls. Production processes and controls are unavoidably complex. Significant public health hazards exist with contaminated products.

6. Evaluation Factors Sterile Products Potential demonstration of adverse effects on safety or effectiveness: Complexity of compounding Facilities and equipment Training Testing and quality assurance

7. Complexity of Compounding Manipulations Processes Controls

8. Facilities and Equipment Highly controlled environment Specialized procedures

9. Training Highly personnel intense Uniform and strict performance standards

10. Testing and Quality Assurance Accomplished when training, testing, facilities and equipment are properly used and monitored

11. Evaluation Factors Sterile Products No reasonable demonstration of adverse effects on safety or effectiveness: Drug Delivery System Drug Formulation and Consistency Bioavailability

12. Tentative Conclusion Sterile products are demonstrably difficult to compound properly if compounded under conditions other than described in USP Chapter

13. Advice Requested Should sterile products not compounded in accordance with USP Chapter be on the list of drugs that are difficult to compound? Is USP Chapter an appropriate standard? Should compliance with USP Chapter be required for compounding relatively low-risk sterile products from sterile components?