Application Note

The Benefits Of Terminal Sterilization Of APIs And Pharmaceutical Fillers

Source: STERIS Corporation

Any company producing a healthcare product with the expectation of sterility is eventually faced with the same questions. Can my product be terminally sterilized? If yes, by what method? Will a traditional, well documented method like gamma irradiation, electron beam, ethylene oxide, heat (dry or moist) or a more non traditional, even novel approach provide the assurance I must have and still provide the product performance and safety needed?

Why Irradiation?

  1. Effectiveness. Well understood mechanism of providing microbiocidal effects.
  2. Documentation. Published, accepted methods for setting an appropriate dose and sterility assurance levels.
  3. Costs. Avoids or reduces costs, time, equipment validation and equipment maintenance to manufacture the product in an appropriate class of clean room. Basically, full sterile manufacture is not needed.
  4. Locations for sterilization available world wide and turn times are rapid. 4. Adds no moisture to product which can lead to reduced stability.
  5. Adds no excess heat (as with autoclaving or dry heat). Heat may also affect stability.
  6. Published options for dose setting have expanded in recent years to give more options, especially on low minimum doses.
  7. Adaptable to small volume products with special handling conditions.
  8. Industry experience, expanded search capabilities in review of published data and suggestions through web accessibility of even very old articles.
  9. Leaves no residuals.
  10. Useful for product that cannot be filtered effectively.

The best advice in this area is always to start early. This is critical since validation data can be obtained in development studies and clinical trial batch production. Also, if it does not work, other options can be considered early. Decisions made with the sterilization method in mind may limit problems later. Even simple choices on a final format or vehicle of delivery may be given proactive consideration if the sterilization process is also considered. Remember, an irradiated drug is considered potentially a different drug than the un-irradiated version. Testing the effectiveness, stability and impurities of an un-irradiated version means additional testing if you do not test irradiated material. Testing early avoids wasted time getting required data.