– How Does One Determine Whether the Product Withstands a Thermal Process That Is Encountered in Moist Heat Sterilization?
– Expectations of Regulatory Agencies Concerning Sterilization of the Solution and Cycle Selection on the Basis of Solution Selection—Development Studies That Need to Be Conducted
– DEFINING REQUIREMENTS
– SELECTION OF A MOIST HEAT STERILIZATION PROCESS
– CONTAINER THERMAL MAPPING: DETERMINING THE SLOWEST-TO-HEAT ZONE
– HOW MUCH LETHALITY IS ENOUGH?
– What Is the Purpose of the D- and z-values?
– Determining the Minimum Microbial Lethality
– Determination of the Probability of Survival for Bioburden
– DETERMINATION OF THE REQUIRED STERILIZATION PROCESS TIME (IN MINUTES OF FO) OR CYCLE DEFINITION (LOAD PROBE CONTROLLED CYCLES)
-Required Sterilization Process Time
– Cycle Definition (Product Penetration Controlled Cycles, i.e., controlled by Fo values in solution filled containers)
– THE CONTAINER/CLOSURE SYSTEM
– True Fo Cannot Be Calculated at Closure Sites
– Regulatory Expectations for Container/Closure Challenge Data
– THE MASTER SOLUTION—BIOLOGICAL CHALLENGES
– How Does One Select the Master Solution?
– Special Considerations Related to the Design of the Subprocess Solution Challenge
– CALCULATION OF THE REQUIRED HEAT HISTORY FOR PROCESSES AT TEMPERATURES OTHER THAN 121°C
– FRACTIONAL OR HALF-CYCLE DEVELOPMENT APPROACHES
– CONTAINER CLOSURE INTEGRITY TESTING
– THE MASTER SOLUTION—HEAT PENETRATION
– The Master Equipment Challenge
– What Thermal Distribution and Penetration Data Are Expected?
Heat Penetration (Thermoprobed Product)
Temperature Distribution Studies
Cycle Come-Up Time or Heat-Up Time*
Calculation of Cooling Times
LOADING PATTERNS AND CONFIGURATIONS
STERILIZATION AND INTEGRITY OF FILTERS
COOLING WATER EVALUATIONS
Development of an appropriate sterilization cycle is difficult. The development of an efficacious and yet economic sterilization process is one of the most critical phases of a product development process. This chapter is intended to provide some guidance on the topic. However, each site needs to have an established cycle development program that takes into account the facilities and equipment actually used. An example of a cycle development standard procedure is included in Appendix B. In regulatory inspections, it is becoming more common for field inspectors to also ask for data that have been submitted in support of submissions. The expectation is that the technical personnel at the facility understand why the specific sterilization parameters were selected for the sterilization process. This demands a knowledge of both microbiology and engineering principles.
Courtesy of DHI Publications.