Sterilization Validation and Routine Operation Handbook (2001): Radiation

Rationale for Validating Sterilization Processes 
Characterization of Radiation Processes 
o Physical Characteristics of Radiation 
o Facility Design 
o Effects of Radiation on Microorganisms 
o System Operations 
o Critical Process Parameters 
o Dose Distribution 
o Dosimeters 
o Dose Mapping 
Contract Sterilization
o Selection of the Sterilization Facility 
o Obtain a Written Contract 
o Verification of Validation 
o Routine Processing
Prevalidation Planning 
o Product and Package Materials Evaluation 
o Accelerated Aging 
o Establishment and Maintenance of Product Families
o Grouping into Product Families 
o Selection of Family Representative 
o Selection of a Sample Item Portion (SIP) 
o Sterility Assurance Levels (SAL)
Microbiological Considerations 
o Evaluation of Product Bioburden 
o Evaluation of Bioburden Data
o Bioburden Isolates 
o Product Sterility Testing 
o Troubleshooting Microbiological Failures
Sterilization Support Testing 
o Selection of a Test Laboratory and Test Methods 
o Environmental Monitoring and Control 
o Biocompatibility Testing 
o Bacterial Endotoxin and Pyrogen Testing 
The Validation Protocol
Outline of the Sterilization Validation 
o Product and Packaging Materials Evaluation 
o Equipment Qualification and Documentation 
o Sterilization Dose Selection 
o Dose Audit 
o Dose Augmentation 
o Selection of a Sterilization Dose for a Single Production Batch
o Alternate Sampling Plans for Dose Verification and Audit 
Final Report 
Routine Monitoring and Control 
o Adopting a Device into a Validated Sterilization System 
o Dose Audit Failure
o Frequency of Sterilization Dose Audits
Appendices 
o Contract Radiation Sterilization Facilities in the United States 
o Method 1 Dose Verification 
o Method 1 Quarterly Dose Audit 
o Worked Example for Method 1 
o Method 2A Dose Validation 
o Worked Example for Single Product Batch (SIP