Changes in the use and requirements of Biological Indicators

In the latest issue of “Pharmeuropa”, European Pharmacopoeia (Ph. Eur.) has published a new draft chapter 5.1.2. Biological Indicators. Also within this issue, you will find an explanatory scientific publication, written by Dr. Hans van Doorne and Dr. Klaus Haberer in the name of Expert Group 1 Microbiology of Ph. Eur. 


In detail, the new position of Ph. Eur. Concerning this chapter has been developed to correct the following problems points in the use of Biological Indicators:


  • The current monograph gives a minimum D-value for Bioindicator resistance to the sterilisation process, but it does not recommend an upper limit. This may lead to uncertainties for the user, should surviving Biological Indicators remain after the sterilization process.
  • The present chapter 5.1.2 requires inactivation of all exposed Bioindicators to validate the effectiveness of a sterilization process. However, Biological Indicators presently found in the market are frequently too resistant to be inactivated Standard Sterilization Process of  the Pharm. Eur. with a sufficient safety margin. Hence, the requirement of complete inactivation is scientifically incorrect and cannot be retained.
  • The present chapter does not offer guidance with regard to the validation of other sterilization processes than the standard process at 121 °C whereas EMA accepts different processes with F0 of at least 8 minutes.
  • There is a lack of correlation between the physical and microbiological validation of sterilization processes in the current chapter.


The new chapter will contain the requirement to match physical expectations and effectiveness of microbiological inactivation of a sterilization processes in the hands of the user of Biological indicators. Bioindicators will be expected to be resistant enough to pose a significant challenge to the sterilization method. Suitability of the Bioindicators should be determined by from the initial spore count and the D-Value. The new approach will accept some survivors after exposure to sterilizing conditions, if this can be expected from the resistance characteristics of the used Bioindicators.