The Bugs Don't Lie.

Sterilization is a critical process in the preparation of many drug products. Its execution and validation are addressed in numerous regulatory, pharmacopeial, and industry documents. EMA Annex 1: Manufacture of Sterile Medicinal Products stands alone in giving clear preference to physical measurements over those obtained from biological indicators. This paper reviews principles behind sterilization processes outlining the differences between physical and biological measurements as well as their relationship to each other. The assumptions associated with the use of physical measurement are explored and their derivation from microbiological results is traced with the intent of reaffirming the primacy of biological evidence. The arguments and objections to the use of biological indicators in sterilization are reviewed and deconstructed. Sterilization validation is required by regulatory agencies around the globe. The accepted principles are derived from those originally established in the United States and the United Kingdom during the 1970s. Unfortunately, these have evolved into conflicting expectations. The U.K. placed greater emphasis on physical measurements initially in HTM-10, and this is reflected in the European Medicines Agency's Annex 1 statements for their preeminence over biological data. Practices, primarily in the U.S., give preference to microbiological challenges as confirmation of lethality. This paper reviews sterilization fundamentals and describes the relationship between physical and biological data. It critiques the various arguments for the superiority of physical measurements and supports why microbiological evidence should take precedence.