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

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

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

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

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.

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

Complexity of Compounding Manipulations Processes Controls

Facilities and Equipment Highly controlled environment Specialized procedures

Training Highly personnel intense Uniform and strict performance standards

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

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

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

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?