Non-heat terminal sterilization of controlled released material

Presentation overview

• A balance must be achieved between the need to maintain a safe, stable and efficacious product while providing sufficient lethality to attain a minimum level of sterility assurance
• No sterilization method should be considered exempt

Material perspective

• Sterilizing processes should be a compromise between the degradation effect on the materials and destruction of microorganisms
• A sterilization process that destroys all microorganisms, but renders the item being sterilized unfit for use is of no value
• The sterilization process and the specific product, formulation and container must all be suited to each other
• There are few universal answers, and some of those that appear to be broadly applicable may be wrong.

Sterilization Methods (ranked by estimated material effect)

• Sterilization by Filtration
• Chemical Sterilization
• Includes aldehydes, oxidizers, halides, acids, bases
•Gas Sterilization
• Includes ETO, Chlorine Dioxide, Ozone
•Vapor Sterilization
• Includes H2O2, and Peracetic acid Radiation Sterilization
• Steam Sterilization
•Dry Heat Sterilization

Sterilization Methods (effect & issue)

• Sterilization by Filtration                                                                                                                                                      Must be a solution, likely requires aseptic processing                                                                                                             to manufacture a dosage form.

• Chemical (Liquid phase) Sterilization-Strong acids / bases, post                                                                                          Process neutralization required, won’t penetrate solids

• Chemical (Gas Phase) Sterilization                                                                                                                                          Potent chemicals, won’t penetrate solids

• Vapor (BiPhasic) Sterilization                                                                                                                                                    Poorly suited – prefer liquid or gas systems for ease of use / validation

• Radiation Sterilization                                                                                                                                                                Method of choice?, penetration varies with method, new methods and ideas possible

• Steam Sterilization                                                                                                                                                                        Heat effects can be extreme, new ideas possible

• Dry Heat Sterilization                                                                                                                                                                    Heat effects are always extreme, few real opportunities

• (Emerging Methods)                                                                                                                                                                      Effective, but may require extensive support for implementation, material effects are largely unstudied.

Sterilization & Penetration

• Little or no penetration
• Chemical Sterilization
• Vapor Sterilization
• Some penetration
• Gas Sterilization
• Steam Sterilization
• Good Penetration
• Dry Heat Sterilization
• Radiation Sterilization